Back to resultsCombining Lovastatin and a Parent-Implemented Language Intervention for Fragile X Syndrome
Primary Purpose
Fragile X Syndrome, Genetic Diseases
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Lovastatin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fragile X Syndrome focused on measuring Fra(X) Syndrome, Trinucleotide Repeat Expansion, Fragile X Syndrome, Fragile X Mental Retardation Syndrome, Intellectual Disability, Parent Implemented Language Intervention (PILI), FXS, Mental Retardation, X-linked, Genetic Diseases, X-linked, Neurobehavioral Manifestations, Chromosome Disorders
Eligibility Criteria
Inclusion Criteria:
- Documentation of a full mutation with absence or deficient FMRP levels.
- Males and females ages 10 through 17 years
- Willingness of potential study participant as well as a parent or caretaker to participate in the protocol.
- Speech is the primary means of communication with three-word or longer utterances used on a daily basis.
- Intelligence quotient (IQ) ≤70 as measured by the Leiter- R.
- Sexually active women of childbearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative qualitative serum β-human chorionic growth hormone (β-HCG) or urine pregnancy test collected at the initial screening visit.
Exclusion Criteria:
- Persons who do not speak English.
- Changes in any medications (including investigational medications) within the last month (4 weeks). All concomitant medications must have been on a stable course for at least 4 weeks prior to enrollment into the study and maintain stability throughout the course of the study.
- Changes in behavioral therapy or educational programming during the study. This does not include scheduled school holidays.
- Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk.
- Patients who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study or displaying clinically significant abnormalities in safety assessments at screening.
- Patients on prohibited medications
- History of recurrent status epilepticus.
- Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial.
- Subjects unwilling to abstain from alcoholic beverages during the trial.
- Subjects who are actively suicidal.
Sites / Locations
- UC Davis MIND Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Lovastatin and PILI
Placebo and PILI
Arm Description
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with study medication Lovastatin.
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with placebo.
Outcomes
Primary Outcome Measures
Expressive Language Sample Composite Score in the Home
The primary outcome reflects the diversity of vocabulary used. Higher scores reflect more skill. The lowest possible value is zero. No theoretical maximum can be defined because the wordless picture books can lead to a large and indeterminate set of options for the amount of talk and the vocabulary used. In a previous study of a nonpharmacological intervention, the range at baseline was 9-177, and at post-treatment, the range for the combined treated and nontreated groups was 23-214, although these values were not corrected for the number of C-units produced (McDuffie at el. 2018 Developmental Neurorehabilitation).
Expressive Language Sample Composite Score in the Home
The primary outcome reflects the diversity of vocabulary used. Higher scores reflect more skill. The lowest possible value is zero. No theoretical maximum can be defined because the wordless picture books can lead to a large and indeterminate set of options for the amount of talk and the vocabulary used. In a previous study of a nonpharmacological intervention, the range at baseline was 9-177, and at post-treatment, the range for the combined treated and nontreated groups was 23-214, although these values were not corrected for the number of C-units produced (McDuffie at el. 2018 Developmental Neurorehabilitation).
Secondary Outcome Measures
FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale
The ABC-C is a 58-item caregiver-rated behavior scale used to examine treatment effects on challenging behaviors for individuals with FXS in the following domains: (1) irritability; (2) lethargy/social withdrawal; (3) stereotypic behavior; (4) hyperactivity; and (5) inappropriate speech. Caregiver rates the subject's behavior as follows: 0 = not a problem, l = the behavior is a problem but slight in degree, 2 = the problem is moderately serious, 3 = the problem is severe in degree. Sansone et al. (2012) further subdivided social withdrawal to rate social avoidance in FXS. The subscale includes 4 items which were originally part of the Lethargy/Withdrawal subscale. This subscale captures core aspects of the FXS phenotype related to gaze avoidance, social ''escape'' behaviors, and social anxiety. Subscale score ranges from 0 to 12, higher scores reflect a more problematic behavior.
FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale
The ABC-C is a 58-item caregiver-rated behavior scale used to examine treatment effects on challenging behaviors for individuals with FXS in the following domains: (1) irritability; (2) lethargy/social withdrawal; (3) stereotypic behavior; (4) hyperactivity; and (5) inappropriate speech. Caregiver rates the subject's behavior as follows: 0 = not a problem, l = the behavior is a problem but slight in degree, 2 = the problem is moderately serious, 3 = the problem is severe in degree. Sansone et al. (2012) further subdivided social withdrawal to rate social avoidance in FXS. The subscale includes 4 items which were originally part of the Lethargy/Withdrawal subscale. This subscale captures core aspects of the FXS phenotype related to gaze avoidance, social ''escape'' behaviors, and social anxiety. Subscale score ranges from 0 to 12, higher scores reflect a more problematic behavior. Shown here are the ABC social avoidance subscale mean scores from the 10-weeks follow-up visit.
FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale
The ABC-C is a 58-item caregiver-rated behavior scale used to examine treatment effects on challenging behaviors for individuals with FXS in the following domains: (1) irritability; (2) lethargy/social withdrawal; (3) stereotypic behavior; (4) hyperactivity; and (5) inappropriate speech. Caregiver rates the subject's behavior as follows: 0 = not a problem, l = the behavior is a problem but slight in degree, 2 = the problem is moderately serious, 3 = the problem is severe in degree. Sansone et al. (2012) further subdivided social withdrawal to rate social avoidance in FXS. The subscale includes 4 items which were originally part of the Lethargy/Withdrawal subscale. This subscale captures core aspects of the FXS phenotype related to gaze avoidance, social ''escape'' behaviors, and social anxiety. Subscale score ranges from 0 to 12, higher scores reflect a more problematic behavior. Shown are the ABC social avoidance subscale mean scores from the 20-weeks end-of-study visit.
Clinical Global Impression- Severity (CGI-S)
A clinician rated scale utilizing history from the parents or caregiver and incorporating it into a clinical rating for severity. The CGI-S was used at the pre-treatment assessment to judge symptom severity. The 7-point scale ranges from: 1 = Normal; 2 = Borderline Ill; 3 = Mildly Ill; 4 = Moderately Ill; 5 = Markedly Ill; 6 = Severely Ill; and 7 = Extremely Ill. Therefore, the higher the score, the greater the severity of the patient's illness. Shown here are the CGI-S mean scores from the baseline visit.
Clinical Global Impression-Improvement (CGI-I) Scale
A clinician rated scale utilizing history from the parents or caregiver and incorporating it into a clinical rating to assess for overall therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the overall improvement as rated by the clinician. The CGI-I was used at the 10 week and 20 week visits. Shown here are the CGI-I mean scores from the 10-weeks end-of-study visit.
Clinical Global Impression-Improvement (CGI-I) Scale
A clinician rated scale utilizing history from the parents or caregiver and incorporating it into a clinical rating to assess for overall therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the overall improvement as rated by the clinician. The CGI-I was used at the 10 week and 20 week visits. Shown here are the CGI-I mean scores from the 20-weeks end-of-study visit.
Visual Analog Scale (VAS) - Spoken Language Impairment
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Spoken Language Impairment scale, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Visual Analog Scale (VAS) - Spoken Language Impairment
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Spoken Language Impairment scale, at 10-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Visual Analog Scale (VAS) - Spoken Language Impairment
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Spoken Language Impairment scale, at 20-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Visual Analog Scale (VAS) - Social Impairment
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Social Impairment scale, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Visual Analog Scale (VAS) - Social Impairment
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Social Impairment scale, at 10-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Visual Analog Scale (VAS) - Social Impairment
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Social Impairment scale, at 20-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Full Information
NCT ID
NCT02642653
First Posted
December 21, 2015
Last Updated
August 22, 2019
Sponsor
University of California, Davis
1. Study Identification
Unique Protocol Identification Number
NCT02642653
Brief Title
Combining Lovastatin and a Parent-Implemented Language Intervention for Fragile X Syndrome
Official Title
Combining Lovastatin and a Parent-Implemented Language Intervention in a Multimodal Treatment for Fragile X Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
January 2016 (Actual)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
July 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to test the efficacy of a 20 week multi-modal treatment comprised of lovastatin or placebo, and the Parent-implemented Language Intervention (PILI) in children with fragile X syndrome (FXS). Children will be randomized to drug or placebo in a double-blind design with all participating in the PILI. The primary endpoint will be to measure improvements in spoken language and behavior among lovastatin-treated than placebo treated participants.
Detailed Description
This is the first multi-modal treatment to combine a targeted treatment for FXS, lovastatin, with an innovative parent-implemented intervention (PILI) targeting language and challenging behavior delivered through telehealth technology.The hypothesis is that targeted treatments will be more effective when applied in combination with PILI. Examination of whether changes in the activity of key pathways/proteins influenced by fragile X mental retardation protein (FMRP) (the mitogen-activated protein kinase (ERK) and MMP-9) are biomarkers of treatment responsiveness. Because lovastatin is also an anti-inflammatory, characterization of MEK/ERK signaling in peripheral immune cells both pre- and post- treatment will be carried out to determine whether levels of these signaling molecules are predictive biomarkers of treatment response. It is hypothesized that those individuals with elevated inflammatory cytokine profiles will be most responsive to lovastatin treatment. Once modeled in FXS, results from these studies can then be applied to other neurodevelopmental disorders including RASopathies.
The behavioral component of the proposed multi-modal treatment will be a Parent-implemented Intervention (PILI) that targets improvements in spoken language and challenging behavior for 10- to 17-year-olds with FXS by increasing parental verbal responsiveness (PVR) within picture-book based story-telling episodes. Parents will be encouraged to use the targeted strategies in other everyday interactions with their child. The intervention will be delivered to parents in their homes by way of video teleconferencing (VTC). Participants will be randomly assigned to receive the behavioral intervention alone or in combination with Lovastatin.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome, Genetic Diseases
Keywords
Fra(X) Syndrome, Trinucleotide Repeat Expansion, Fragile X Syndrome, Fragile X Mental Retardation Syndrome, Intellectual Disability, Parent Implemented Language Intervention (PILI), FXS, Mental Retardation, X-linked, Genetic Diseases, X-linked, Neurobehavioral Manifestations, Chromosome Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lovastatin and PILI
Arm Type
Active Comparator
Arm Description
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with study medication Lovastatin.
Arm Title
Placebo and PILI
Arm Type
Placebo Comparator
Arm Description
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with placebo.
Intervention Type
Drug
Intervention Name(s)
Lovastatin
Other Intervention Name(s)
Mevacor
Intervention Description
Once per day dosing
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Once per day dosing
Primary Outcome Measure Information:
Title
Expressive Language Sample Composite Score in the Home
Description
The primary outcome reflects the diversity of vocabulary used. Higher scores reflect more skill. The lowest possible value is zero. No theoretical maximum can be defined because the wordless picture books can lead to a large and indeterminate set of options for the amount of talk and the vocabulary used. In a previous study of a nonpharmacological intervention, the range at baseline was 9-177, and at post-treatment, the range for the combined treated and nontreated groups was 23-214, although these values were not corrected for the number of C-units produced (McDuffie at el. 2018 Developmental Neurorehabilitation).
Time Frame
Baseline
Title
Expressive Language Sample Composite Score in the Home
Description
The primary outcome reflects the diversity of vocabulary used. Higher scores reflect more skill. The lowest possible value is zero. No theoretical maximum can be defined because the wordless picture books can lead to a large and indeterminate set of options for the amount of talk and the vocabulary used. In a previous study of a nonpharmacological intervention, the range at baseline was 9-177, and at post-treatment, the range for the combined treated and nontreated groups was 23-214, although these values were not corrected for the number of C-units produced (McDuffie at el. 2018 Developmental Neurorehabilitation).
Time Frame
20 weeks
Secondary Outcome Measure Information:
Title
FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale
Description
The ABC-C is a 58-item caregiver-rated behavior scale used to examine treatment effects on challenging behaviors for individuals with FXS in the following domains: (1) irritability; (2) lethargy/social withdrawal; (3) stereotypic behavior; (4) hyperactivity; and (5) inappropriate speech. Caregiver rates the subject's behavior as follows: 0 = not a problem, l = the behavior is a problem but slight in degree, 2 = the problem is moderately serious, 3 = the problem is severe in degree. Sansone et al. (2012) further subdivided social withdrawal to rate social avoidance in FXS. The subscale includes 4 items which were originally part of the Lethargy/Withdrawal subscale. This subscale captures core aspects of the FXS phenotype related to gaze avoidance, social ''escape'' behaviors, and social anxiety. Subscale score ranges from 0 to 12, higher scores reflect a more problematic behavior.
Time Frame
Baseline
Title
FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale
Description
The ABC-C is a 58-item caregiver-rated behavior scale used to examine treatment effects on challenging behaviors for individuals with FXS in the following domains: (1) irritability; (2) lethargy/social withdrawal; (3) stereotypic behavior; (4) hyperactivity; and (5) inappropriate speech. Caregiver rates the subject's behavior as follows: 0 = not a problem, l = the behavior is a problem but slight in degree, 2 = the problem is moderately serious, 3 = the problem is severe in degree. Sansone et al. (2012) further subdivided social withdrawal to rate social avoidance in FXS. The subscale includes 4 items which were originally part of the Lethargy/Withdrawal subscale. This subscale captures core aspects of the FXS phenotype related to gaze avoidance, social ''escape'' behaviors, and social anxiety. Subscale score ranges from 0 to 12, higher scores reflect a more problematic behavior. Shown here are the ABC social avoidance subscale mean scores from the 10-weeks follow-up visit.
Time Frame
10 weeks
Title
FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale
Description
The ABC-C is a 58-item caregiver-rated behavior scale used to examine treatment effects on challenging behaviors for individuals with FXS in the following domains: (1) irritability; (2) lethargy/social withdrawal; (3) stereotypic behavior; (4) hyperactivity; and (5) inappropriate speech. Caregiver rates the subject's behavior as follows: 0 = not a problem, l = the behavior is a problem but slight in degree, 2 = the problem is moderately serious, 3 = the problem is severe in degree. Sansone et al. (2012) further subdivided social withdrawal to rate social avoidance in FXS. The subscale includes 4 items which were originally part of the Lethargy/Withdrawal subscale. This subscale captures core aspects of the FXS phenotype related to gaze avoidance, social ''escape'' behaviors, and social anxiety. Subscale score ranges from 0 to 12, higher scores reflect a more problematic behavior. Shown are the ABC social avoidance subscale mean scores from the 20-weeks end-of-study visit.
Time Frame
20 weeks
Title
Clinical Global Impression- Severity (CGI-S)
Description
A clinician rated scale utilizing history from the parents or caregiver and incorporating it into a clinical rating for severity. The CGI-S was used at the pre-treatment assessment to judge symptom severity. The 7-point scale ranges from: 1 = Normal; 2 = Borderline Ill; 3 = Mildly Ill; 4 = Moderately Ill; 5 = Markedly Ill; 6 = Severely Ill; and 7 = Extremely Ill. Therefore, the higher the score, the greater the severity of the patient's illness. Shown here are the CGI-S mean scores from the baseline visit.
Time Frame
Baseline
Title
Clinical Global Impression-Improvement (CGI-I) Scale
Description
A clinician rated scale utilizing history from the parents or caregiver and incorporating it into a clinical rating to assess for overall therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the overall improvement as rated by the clinician. The CGI-I was used at the 10 week and 20 week visits. Shown here are the CGI-I mean scores from the 10-weeks end-of-study visit.
Time Frame
10 weeks
Title
Clinical Global Impression-Improvement (CGI-I) Scale
Description
A clinician rated scale utilizing history from the parents or caregiver and incorporating it into a clinical rating to assess for overall therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the overall improvement as rated by the clinician. The CGI-I was used at the 10 week and 20 week visits. Shown here are the CGI-I mean scores from the 20-weeks end-of-study visit.
Time Frame
20 weeks
Title
Visual Analog Scale (VAS) - Spoken Language Impairment
Description
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Spoken Language Impairment scale, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame
Baseline
Title
Visual Analog Scale (VAS) - Spoken Language Impairment
Description
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Spoken Language Impairment scale, at 10-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame
10 weeks
Title
Visual Analog Scale (VAS) - Spoken Language Impairment
Description
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Spoken Language Impairment scale, at 20-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame
20 weeks
Title
Visual Analog Scale (VAS) - Social Impairment
Description
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Social Impairment scale, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame
Baseline
Title
Visual Analog Scale (VAS) - Social Impairment
Description
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Social Impairment scale, at 10-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame
10-weeks
Title
Visual Analog Scale (VAS) - Social Impairment
Description
The measure was used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 10-weeks and 20-weeks visits. The calculated distance in cm between the marks drawn at the baseline and follow-up visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Social Impairment scale, at 20-weeks. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame
20-weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Documentation of a full mutation with absence or deficient FMRP levels.
Males and females ages 10 through 17 years
Willingness of potential study participant as well as a parent or caretaker to participate in the protocol.
Speech is the primary means of communication with three-word or longer utterances used on a daily basis.
Intelligence quotient (IQ) ≤70 as measured by the Leiter- R.
Sexually active women of childbearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative qualitative serum β-human chorionic growth hormone (β-HCG) or urine pregnancy test collected at the initial screening visit.
Exclusion Criteria:
Persons who do not speak English.
Changes in any medications (including investigational medications) within the last month (4 weeks). All concomitant medications must have been on a stable course for at least 4 weeks prior to enrollment into the study and maintain stability throughout the course of the study.
Changes in behavioral therapy or educational programming during the study. This does not include scheduled school holidays.
Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk.
Patients who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study or displaying clinically significant abnormalities in safety assessments at screening.
Patients on prohibited medications
History of recurrent status epilepticus.
Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial.
Subjects unwilling to abstain from alcoholic beverages during the trial.
Subjects who are actively suicidal.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Randi J Hagerman, MD
Organizational Affiliation
UC Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
UC Davis MIND Institute
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32316911
Citation
Thurman AJ, Potter LA, Kim K, Tassone F, Banasik A, Potter SN, Bullard L, Nguyen V, McDuffie A, Hagerman R, Abbeduto L. Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome. J Neurodev Disord. 2020 Apr 22;12(1):12. doi: 10.1186/s11689-020-09315-4.
Results Reference
derived
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Combining Lovastatin and a Parent-Implemented Language Intervention for Fragile X Syndrome
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