Back to resultsA Double-blind, Placebo Controlled Trial of Risperidone for the Treatment of Anorexia Nervosa
Primary Purpose
Anorexia Nervosa
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Risperidone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Anorexia Nervosa focused on measuring Anorexia Nervosa, Risperidone, Atypical Neuroleptics, Dopamine, Leptin, Body Image, Adolescents
Eligibility Criteria
Inclusion Criteria: Primary Diagnosis of Anorexia Nervosa Female, age 12-21 Active in a level of care for AN at The Children's Hospital, Denver As long as there is a primary dx of AN, co-morbid diagnoses may be included. If taking an antidepressant, must be on a stable dose for 3 weeks prior to entering the study, and dose of antidepressant may not be changed during Phase 1 of the study. If choosing to discontinue antidepressant medication, must be off the medication for 3 weeks prior to beginning the study. If sexually active, must use birth control during the study and have a monthly pregnancy test. Exclusion Criteria: Previous enrollment in this study on a prior admission Previous allergic reaction to risperidone or other atypical neuroleptic Positive pregnancy test Neurologic disorder other than benign essential tremor Taking a psychotropic medication other than antidepressant and discontinuing the medication is not recommended. Active hepatic or renal disease Wards of the state Males
Sites / Locations
- The Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
placebo
risperidone
Arm Description
double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo.
Study is double blind, placebo controlled. This is the subject group on active medication
Outcomes
Primary Outcome Measures
Change in Eating Disorder Inventory-2 Drive for Thinness Subscale (DT)
Eating Disorder Inventory -2 - Subscale : Drive for Thinness Subscale (DT). Lower scores are better on this scale and indicate less cognitive focus on drive for thinness.
The EDI 2 is a 91 item scale with 8 subscales - (Drive for thinness, Bulimia, body dissatisfaction, ineffectiveness, perfection, interpersonal distrust, interoceptive awareness and maturity fears.). The DT subscale was used for this outcome. Respondents rate each item as "usually , often, sometimes, rarely or never". Subscale scores are computed by summing all item scores for each subscale. There are 7 items in the DT subscale (questions 1,7,11,16,25,32 and 49). the subscale score range is 0-21. The EDI-2 was completed by subjects at baseline and then monthly during study participation (range 0 -18 weeks). Change in the DT subscale score was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Change in Eating Disorder Inventory (EDI)-2 Score for Body Dissatisfaction (BD)
change in Eating Disorder Inventory (EDI) 2-score for Body Dissatisfaction (BD).
Lower scores are better on this scale. Higher scores indicate the subject has greater body dissatisfaction. BD is one of the 8 subscales of the EDI-2. 9 of the 91 questions in the EDI-2 scale constitute this subscale. The score range is 0-27. Subjects completed the EDI-2 at baseline and monthly during study participation (range 0 to 18 weeks). Change in the BD subscale score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Hazard Ratio for Time to Reaching Ease Of Eating Level 3 From Start of Study (Normal Eating Behavior)
The Ease of Eating Scale (EOES) is a 14 item scale which measures Food avoidance behaviors (FABs). The scale is rated by staff observing a subject eating a meal or snack. 0 = normal eating behavior, maximum score 28.
Higher scores indicate more food avoidance behaviors, such as taking small bites, taking > 30 seconds between bites (slow eating), etc.
EOE was completed for each meal a subject ate in the program and scores were averaged for each week in the study and entered in the data base.
Change in EOES score was calculated by evaluating change over time. This measure was only used in Phase 1 of the study, for days the subjects were in the treatment program.
Color A Person Test (CAPT)
Color A Person Test (CAPT) - Subjects color an outlined image of a body to indicate body dissatisfaction (red (5)= very dissatisfied, Yellow, dissatisfied, black, neutral, green satisfied, blue very satisfied (1). The outline is divided into16 sections for scoring. The CAPT was completed at baseline and monthly during study participation.
Total CAPT scores were calculated by adding the total score and dividing by 16. Score range is 1-5. Lower scores indicate less body dissatisfaction.
Change in the CAPT score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Body Image Software (BIS): Average Distortion
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer using the direction to "adjust their image to how they see themselves right now", this determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.
Change in the BIS Average Distortion score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. There are no subscales. The BIS program calculates the difference between their actual image and the size of the image they have adjusted the digital image to based on their perception of "how they see themselves right now"
Body Image Software (BIS): Average Desired Thinness
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to "their desired image". The BIS program calculates the difference between their actual image, and how much they have adjusted the image to represent their "desired image". Accuracy is measured by a smaller score between desired image and actual image.
Change in BIS - Average Desired Thinness score was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. . There are no subscales.
Body Image Software (BIS) - Point of Subjective Equality (PSE)
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to their desired image, and also completes a task that determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.
Change in BIS -PSE was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. Interpreting the PSE is how it compares to a PSE = 0, which is no distortion in body size.
Body Image Software (BIS) - Difference Limen (DL)
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to their desired image, and also completes a task that determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.
Change in BIS-DL was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. There are no subscales. Interpreting the DL occurs by referencing it to DL= 0, which would reflect a total inability to detect size differences, which has never occurred in studies using the BIS program.
Secondary Outcome Measures
Time to Reach 90% Ideal Body Weight (IBW) and Maintain for 1 Month, Stratified by >=80% at Start of Study
The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. These estimates were produced using Kaplan-Meier probabilities. This was measured weekly from 0-18 weeks.
Change in Ratings of Anxiety Symptoms on the Multidimensional Anxiety Scale for Children (MASC)
The Multidimensional Anxiety Scale for Children (MASC) is a self report measure completed by the subject that measures anxiety symptoms.
Higher scores indicate greater anxiety. A score of over 50 is significant for anxiety
Change in MASC scores was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Change in Leptin Levels
Leptin levels were measured by serum blood draws, results reports in nanograms / ml (ng/ml).
Change in Prolactin Levels
Prolactin serum blood levels, measured in nanograms / ml
Time to Reach 90% IBW and Maintain for 1 Month, Stratified by IBW <80% at Start of Study
The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. These estimates were produced using Kaplan-Meier probabilities.
Full Information
NCT ID
NCT00140426
First Posted
August 31, 2005
Last Updated
December 29, 2015
Sponsor
University of Colorado, Denver
Collaborators
Janssen Pharmaceuticals, National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT00140426
Brief Title
A Double-blind, Placebo Controlled Trial of Risperidone for the Treatment of Anorexia Nervosa
Official Title
A Double-blind, Placebo Controlled Trial of Risperidone for the Treatment of Anorexia Nervosa
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
August 2004 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Janssen Pharmaceuticals, National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this pilot study is to determine the safety and efficacy of risperidone for the treatment of anorexia nervosa.
Hypothesis 1: Subjects on risperidone will show a more significant decrease in body image distortion and Eating Disorder Inventory -2 scores than subjects on placebo.
Hypothesis 2: Subjects on risperidone will reach and maintain at or above 90% Ideal body weight sooner than controls.
Detailed Description
The lack of effective medications for the symptoms of anorexia nervosa (AN), combined with early promising findings in case reports (Risperidone and Olanzapine) and one open study of olanzapine have led to increased use of these medications for individuals with AN. This double-blind placebo controlled study of risperidone will attempt to determine if risperidone is effective in decreasing core symptoms of anorexia nervosa and decreasing the length of time required to reach and maintain at or about 90% Ideal body weight. The safety of risperidone in this population will also be examined through monitoring of Extrapyramidal Symptoms, Tardive Dyskinesia, Electrocardiograms's, Resting Energy Expenditure, liver enzymes and other blood chemistry. Other possible variables which may mediate the recovery process or be impacted by risperidone,such as leptin and anxiety symptoms are also being measured.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anorexia Nervosa
Keywords
Anorexia Nervosa, Risperidone, Atypical Neuroleptics, Dopamine, Leptin, Body Image, Adolescents
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
double blind study of risperidone for anorexia nervosa. this is the subject group that receives placebo.
Arm Title
risperidone
Arm Type
Active Comparator
Arm Description
Study is double blind, placebo controlled. This is the subject group on active medication
Intervention Type
Drug
Intervention Name(s)
Risperidone
Other Intervention Name(s)
Risperdal
Intervention Description
risperidone titrated 0.5 to 4 mg over study enrollment. Mean Length of Phase 1 is currently 10 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo - inactive pill
Intervention Description
Comparison of risperidone versus placebo for the treatment of symptoms related to anorexia nervosa.
Primary Outcome Measure Information:
Title
Change in Eating Disorder Inventory-2 Drive for Thinness Subscale (DT)
Description
Eating Disorder Inventory -2 - Subscale : Drive for Thinness Subscale (DT). Lower scores are better on this scale and indicate less cognitive focus on drive for thinness.
The EDI 2 is a 91 item scale with 8 subscales - (Drive for thinness, Bulimia, body dissatisfaction, ineffectiveness, perfection, interpersonal distrust, interoceptive awareness and maturity fears.). The DT subscale was used for this outcome. Respondents rate each item as "usually , often, sometimes, rarely or never". Subscale scores are computed by summing all item scores for each subscale. There are 7 items in the DT subscale (questions 1,7,11,16,25,32 and 49). the subscale score range is 0-21. The EDI-2 was completed by subjects at baseline and then monthly during study participation (range 0 -18 weeks). Change in the DT subscale score was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Time Frame
month
Title
Change in Eating Disorder Inventory (EDI)-2 Score for Body Dissatisfaction (BD)
Description
change in Eating Disorder Inventory (EDI) 2-score for Body Dissatisfaction (BD).
Lower scores are better on this scale. Higher scores indicate the subject has greater body dissatisfaction. BD is one of the 8 subscales of the EDI-2. 9 of the 91 questions in the EDI-2 scale constitute this subscale. The score range is 0-27. Subjects completed the EDI-2 at baseline and monthly during study participation (range 0 to 18 weeks). Change in the BD subscale score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Time Frame
monthly
Title
Hazard Ratio for Time to Reaching Ease Of Eating Level 3 From Start of Study (Normal Eating Behavior)
Description
The Ease of Eating Scale (EOES) is a 14 item scale which measures Food avoidance behaviors (FABs). The scale is rated by staff observing a subject eating a meal or snack. 0 = normal eating behavior, maximum score 28.
Higher scores indicate more food avoidance behaviors, such as taking small bites, taking > 30 seconds between bites (slow eating), etc.
EOE was completed for each meal a subject ate in the program and scores were averaged for each week in the study and entered in the data base.
Change in EOES score was calculated by evaluating change over time. This measure was only used in Phase 1 of the study, for days the subjects were in the treatment program.
Time Frame
weekly up to study endpoint: reaching target weight and maintaining for 1 month
Title
Color A Person Test (CAPT)
Description
Color A Person Test (CAPT) - Subjects color an outlined image of a body to indicate body dissatisfaction (red (5)= very dissatisfied, Yellow, dissatisfied, black, neutral, green satisfied, blue very satisfied (1). The outline is divided into16 sections for scoring. The CAPT was completed at baseline and monthly during study participation.
Total CAPT scores were calculated by adding the total score and dividing by 16. Score range is 1-5. Lower scores indicate less body dissatisfaction.
Change in the CAPT score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Time Frame
monthly
Title
Body Image Software (BIS): Average Distortion
Description
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer using the direction to "adjust their image to how they see themselves right now", this determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.
Change in the BIS Average Distortion score during the study was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. There are no subscales. The BIS program calculates the difference between their actual image and the size of the image they have adjusted the digital image to based on their perception of "how they see themselves right now"
Time Frame
monthly
Title
Body Image Software (BIS): Average Desired Thinness
Description
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to "their desired image". The BIS program calculates the difference between their actual image, and how much they have adjusted the image to represent their "desired image". Accuracy is measured by a smaller score between desired image and actual image.
Change in BIS - Average Desired Thinness score was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. . There are no subscales.
Time Frame
monthly
Title
Body Image Software (BIS) - Point of Subjective Equality (PSE)
Description
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to their desired image, and also completes a task that determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.
Change in BIS -PSE was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. Interpreting the PSE is how it compares to a PSE = 0, which is no distortion in body size.
Time Frame
monthly
Title
Body Image Software (BIS) - Difference Limen (DL)
Description
Body Image Software (BIS) - the subject adjusts a digital image of themselves on the computer to their desired image, and also completes a task that determines their perception of their current image. Accuracy is measured by a smaller score between desired image and actual image.
Change in BIS-DL was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
There are no identifiable minimum/maximum values as there would be in a questionnaire scale. There are no subscales. Interpreting the DL occurs by referencing it to DL= 0, which would reflect a total inability to detect size differences, which has never occurred in studies using the BIS program.
Time Frame
monthly
Secondary Outcome Measure Information:
Title
Time to Reach 90% Ideal Body Weight (IBW) and Maintain for 1 Month, Stratified by >=80% at Start of Study
Description
The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. These estimates were produced using Kaplan-Meier probabilities. This was measured weekly from 0-18 weeks.
Time Frame
weekly
Title
Change in Ratings of Anxiety Symptoms on the Multidimensional Anxiety Scale for Children (MASC)
Description
The Multidimensional Anxiety Scale for Children (MASC) is a self report measure completed by the subject that measures anxiety symptoms.
Higher scores indicate greater anxiety. A score of over 50 is significant for anxiety
Change in MASC scores was calculated using an estimate of change in score between week 0 and week 7 derived from the mixed effect model across all time points.
Time Frame
monthly to study end point
Title
Change in Leptin Levels
Description
Leptin levels were measured by serum blood draws, results reports in nanograms / ml (ng/ml).
Time Frame
Week 0 and week 7
Title
Change in Prolactin Levels
Description
Prolactin serum blood levels, measured in nanograms / ml
Time Frame
week 0 and week 7
Title
Time to Reach 90% IBW and Maintain for 1 Month, Stratified by IBW <80% at Start of Study
Description
The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. These estimates were produced using Kaplan-Meier probabilities.
Time Frame
0 - 18 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Primary Diagnosis of Anorexia Nervosa
Female, age 12-21
Active in a level of care for AN at The Children's Hospital, Denver
As long as there is a primary dx of AN, co-morbid diagnoses may be included.
If taking an antidepressant, must be on a stable dose for 3 weeks prior to entering the study, and dose of antidepressant may not be changed during Phase 1 of the study.
If choosing to discontinue antidepressant medication, must be off the medication for 3 weeks prior to beginning the study.
If sexually active, must use birth control during the study and have a monthly pregnancy test.
Exclusion Criteria:
Previous enrollment in this study on a prior admission
Previous allergic reaction to risperidone or other atypical neuroleptic
Positive pregnancy test
Neurologic disorder other than benign essential tremor
Taking a psychotropic medication other than antidepressant and discontinuing the medication is not recommended.
Active hepatic or renal disease
Wards of the state
Males
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer O Hagman, MD
Organizational Affiliation
University of Colorado, Health Sciences Center and The Children's Hospital, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
21871373
Citation
Hagman J, Gralla J, Sigel E, Ellert S, Dodge M, Gardner R, O'Lonergan T, Frank G, Wamboldt MZ. A double-blind, placebo-controlled study of risperidone for the treatment of adolescents and young adults with anorexia nervosa: a pilot study. J Am Acad Child Adolesc Psychiatry. 2011 Sep;50(9):915-24. doi: 10.1016/j.jaac.2011.06.009. Epub 2011 Aug 5.
Results Reference
derived
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A Double-blind, Placebo Controlled Trial of Risperidone for the Treatment of Anorexia Nervosa
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