search
Back to results

Rapalogues for Autism Phenotype in TSC: A Feasibility Study (RAPT)

Primary Purpose

Tuberous Sclerosis Complex, Self-injury, Autism

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sirolimus
Everolimus
Sponsored by
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberous Sclerosis Complex focused on measuring Tuberous Sclerosis Complex (TSC), self-injury, Autism

Eligibility Criteria

2 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Diagnosed with Tuberous Sclerosis Complex as defined by the revised NIH consensus criteria
  2. Possible autism or autism spectrum disorder and/or possible intellectual disability and/or global developmental delay
  3. Currently displaying disruptive behaviors, such as self-injury and aggression
  4. Seizures or epilepsy with at least one seizure within six months prior to enrollment
  5. 2-30 years of age
  6. English-speaking caregiver if participant is non-verbal.
  7. If individuals are currently being treated with everolimus, they must have been taking it for less than or equal to 6 months.

Exclusion Criteria:

  1. Participants who require live vaccines that are contraindicated with sirolimus will be excluded - bacille Calmette Guerin(BCG), measles-mumps-rubella vaccine(MMR), poliovirus, rotavirus, smallpox, typhoid, varicella, or yellow fever.
  2. Participants who have a history of multiple or severe infections, or reside in a household with anyone who has a chronic, contagious condition will be excluded. Multiple infections will be defined as eight or more lifetime episodes of otitis media or two or more lifetime episodes of bacterial pneumonia. Severe infections will be defined as infections requiring more than one hospital admission for treatment.
  3. Participants with any of the following laboratory abnormalities will be excluded: hematocrit < 27%, absolute neutrophil count(ANC) < 1,500, platelet count < 100,000, serum glutamate oxaloacetate transaminase(SGOT) or serum glutamate pyruvate transaminase (SGPT) > two times normal for age, bilirubin > two times normal for age, alkaline phosphatase > two times normal for age, epidermal growth factor receptor (eGFR) < 30, or evidence of renal failure, hypercholesterolemia.
  4. Participants who have medical contraindications to undergoing an MRI will be excluded.
  5. Participants with devices implanted in the brain will be excluded.
  6. Pregnant participants will be excluded. All young ladies of child bearing potential will have a blood test for pregnancy prior to the start of the study and every study visit for the duration of the study.
  7. Participants who have a history of herpes simplex virus, cytomegalovirus, and/or HIV infection will be excluded

Sites / Locations

  • Kennedy Krieger Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sirolimus or Everolimus

Arm Description

Oral solution or tablet,titrated to therapeutic serum trough range (sirolimus); Oral tablet, titrated to therapeutic serum trough range (everolimus)

Outcomes

Primary Outcome Measures

Number of Participants With Compliance to the Treatment Protocol.
One outcome measurement of feasibility will include family/patient compliance with the treatment protocol, which will be assessed and documented at every study visit and telephone follow-up call, by the physician and/or study team member. This was calculated by calculating dividing the total number of study visits and study assessments completed by the total number of study visits and study assessments indicated by the treatment protocol.
Caregiver Burden
The Caregiver Burden Scale is a standard set of questions which will be used to measure the non-medical impact of TSC on caregivers and how it affects the feasibility of study completion. The Caregiver's Burden Scale (CBS) is a 22-item scale that assess subjectively experienced burden by caregiver's to chronically disabled persons. maximum scores: 88 & Minumum scores: 22 High values represent a worse outcome
Feasibility Measurements of Parental Stress
Measurements of stress will be administered. Specifically, we will use the Parental Stress Index. Quantifying stress, as well as compliance with the study protocol, will allow investigators to objectively assess the feasibility of a larger clinical trial of sirolimus in patients with TSC. Parental stress index maximum score: 180 Parental stress index minimum score: 36 higher raw scores indicate higher levels of stress.

Secondary Outcome Measures

Total Number of Aggressions or Self-injuries
This is the total number of aggressions or self-injuries for all participants.
Cognitive Function as Assessed by the Capute Scale
Score range maximum: 100 Score range minimum: 0 High values represent a high cognitive function Below 70 is abnormal. 70-100 is the normal range.
Repetitive Behavior
Repetitive behavior will be assessed using the Repetitive Behavior Scale - revised, a questionnaire to characterize several domains of repetitive behavior including ritualistic behavior, stereotypic behavior, self-injurious behavior, compulsive behavior, and restricted interests. There are 36 items on the scale. Behaviors are rated on a 4-point scale: 0-Behavior does not occur, 1-Behavior occurs and is a mild problem, 2-Behavior occurs and is a moderate problem, 3-Behavior occurs and is a severe problem. Maximum score: 108 & minimum score: 0 A high score represents the worse outcome
Self-Injury Trauma Scale--SIT Scale
The SIT Scale is a 3-part clinician-completed scale used to quantify visible injuries caused by self-injurious behavior(SIB). Part 1 includes sections to indicate SIB topographies and any evidence of healed injury. In Part 2 evaluators document the location and severity of injury (on a 3-point scale). In Part 3, respective scores from Parts 1 and 2 are summed to obtain a Number Index, a Severity Index, and Estimate of Current Risk. This Scale has been used in research with adults with SIB with inter-rater reliability averaging 85%. Maximum score: 100 Minimum score: 0 High score represent worse outcome.
Frequency of Seizures Assessed by Total Number of Seizures
Parents will be asked to document the frequency of their child's seizures using a manual or electronic (seizuretracker.com) seizure diary. The total number of seizures at baseline for all participants.

Full Information

First Posted
August 7, 2013
Last Updated
March 26, 2021
Sponsor
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01929642
Brief Title
Rapalogues for Autism Phenotype in TSC: A Feasibility Study
Acronym
RAPT
Official Title
Rapalogues for Autism Phenotype in TSC: A Feasibility Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the feasibility and safety of administering rapalogues, sirolimus or everolimus, in participants with Tuberous Sclerosis Complex (TSC) and self-injury and to measure cognitive and behavioral changes, including reduction in autistic symptoms, self-injurious and aggressive behaviors, as well as improvements in cognition across multiple domains of cognitive function.
Detailed Description
This is a feasibility and safety study primarily designed to assess the feasibility and safety of conducting a larger clinical trial with sirolimus in individuals with TSC. The present study will employ an ABA design in which three pediatric participants will be selected to receive baseline medical, developmental, behavioral, and cognitive evaluations, followed by a 26 week administration of sirolimus, repeated baseline assessments at the end of the 26 week treatment phase, and a 4 week titrated withdrawal followed by a 22 week period in which no rapalogue is administered. All participants will again be administered baseline medical, behavioral, and cognitive evaluations at the end of the study in order to compare all evaluations done at baseline, the end of the 26 week treatment, and completion of the study. These comparisons will be done to assess secondary outcomes that include reductions in autistic symptoms, self-injury, and aggression, as well as improvements in cognitive function across multiple domains. Furthermore, administration of the secondary outcome measures will also allow us to better understand the sensitivity of these measures in patients with TSC during the course of a clinical trial. Families of potentially eligible children who express interest in the study and meet prescreening criteria will be invited to attend a screening visit to determine eligibility, inclusion/exclusion criteria, and availability for eight additional study visits. Prior to enrollment, informed consent will be obtained from the parent or legal guardian. Investigators will use the methods of analysis of single-subject research (ABA design, where first A represents baseline, B represents treatment, and A represents reversal of treatment. The analysis will focus on each of the 3 subjects separately. Data on feasibility and safety (primary outcome) and on frequency of disruptive behavior (secondary outcome) will be plotted and visually inspected to detect any temporal changes by phase: 1. Baseline, 2. Treatment, 3. After treatment. Data in each phase will be summarized as mean +/- standard deviation (SD). We will use the summary data to assess the potential effect of the intervention. Consistency of the effect will be examined across the 3 study participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis Complex, Self-injury, Autism
Keywords
Tuberous Sclerosis Complex (TSC), self-injury, Autism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sirolimus or Everolimus
Arm Type
Experimental
Arm Description
Oral solution or tablet,titrated to therapeutic serum trough range (sirolimus); Oral tablet, titrated to therapeutic serum trough range (everolimus)
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune, Rapamycin
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor
Primary Outcome Measure Information:
Title
Number of Participants With Compliance to the Treatment Protocol.
Description
One outcome measurement of feasibility will include family/patient compliance with the treatment protocol, which will be assessed and documented at every study visit and telephone follow-up call, by the physician and/or study team member. This was calculated by calculating dividing the total number of study visits and study assessments completed by the total number of study visits and study assessments indicated by the treatment protocol.
Time Frame
Change from baseline to EOT visit 12 week 53
Title
Caregiver Burden
Description
The Caregiver Burden Scale is a standard set of questions which will be used to measure the non-medical impact of TSC on caregivers and how it affects the feasibility of study completion. The Caregiver's Burden Scale (CBS) is a 22-item scale that assess subjectively experienced burden by caregiver's to chronically disabled persons. maximum scores: 88 & Minumum scores: 22 High values represent a worse outcome
Time Frame
Change from baseline to EOT visit 12 week 53
Title
Feasibility Measurements of Parental Stress
Description
Measurements of stress will be administered. Specifically, we will use the Parental Stress Index. Quantifying stress, as well as compliance with the study protocol, will allow investigators to objectively assess the feasibility of a larger clinical trial of sirolimus in patients with TSC. Parental stress index maximum score: 180 Parental stress index minimum score: 36 higher raw scores indicate higher levels of stress.
Time Frame
Change from baseline to EOT visit 12 week 53
Secondary Outcome Measure Information:
Title
Total Number of Aggressions or Self-injuries
Description
This is the total number of aggressions or self-injuries for all participants.
Time Frame
1 year
Title
Cognitive Function as Assessed by the Capute Scale
Description
Score range maximum: 100 Score range minimum: 0 High values represent a high cognitive function Below 70 is abnormal. 70-100 is the normal range.
Time Frame
1 year
Title
Repetitive Behavior
Description
Repetitive behavior will be assessed using the Repetitive Behavior Scale - revised, a questionnaire to characterize several domains of repetitive behavior including ritualistic behavior, stereotypic behavior, self-injurious behavior, compulsive behavior, and restricted interests. There are 36 items on the scale. Behaviors are rated on a 4-point scale: 0-Behavior does not occur, 1-Behavior occurs and is a mild problem, 2-Behavior occurs and is a moderate problem, 3-Behavior occurs and is a severe problem. Maximum score: 108 & minimum score: 0 A high score represents the worse outcome
Time Frame
1 year
Title
Self-Injury Trauma Scale--SIT Scale
Description
The SIT Scale is a 3-part clinician-completed scale used to quantify visible injuries caused by self-injurious behavior(SIB). Part 1 includes sections to indicate SIB topographies and any evidence of healed injury. In Part 2 evaluators document the location and severity of injury (on a 3-point scale). In Part 3, respective scores from Parts 1 and 2 are summed to obtain a Number Index, a Severity Index, and Estimate of Current Risk. This Scale has been used in research with adults with SIB with inter-rater reliability averaging 85%. Maximum score: 100 Minimum score: 0 High score represent worse outcome.
Time Frame
1 year
Title
Frequency of Seizures Assessed by Total Number of Seizures
Description
Parents will be asked to document the frequency of their child's seizures using a manual or electronic (seizuretracker.com) seizure diary. The total number of seizures at baseline for all participants.
Time Frame
at baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosed with Tuberous Sclerosis Complex as defined by the revised NIH consensus criteria Possible autism or autism spectrum disorder and/or possible intellectual disability and/or global developmental delay Currently displaying disruptive behaviors, such as self-injury and aggression Seizures or epilepsy with at least one seizure within six months prior to enrollment 2-30 years of age English-speaking caregiver if participant is non-verbal. If individuals are currently being treated with everolimus, they must have been taking it for less than or equal to 6 months. Exclusion Criteria: Participants who require live vaccines that are contraindicated with sirolimus will be excluded - bacille Calmette Guerin(BCG), measles-mumps-rubella vaccine(MMR), poliovirus, rotavirus, smallpox, typhoid, varicella, or yellow fever. Participants who have a history of multiple or severe infections, or reside in a household with anyone who has a chronic, contagious condition will be excluded. Multiple infections will be defined as eight or more lifetime episodes of otitis media or two or more lifetime episodes of bacterial pneumonia. Severe infections will be defined as infections requiring more than one hospital admission for treatment. Participants with any of the following laboratory abnormalities will be excluded: hematocrit < 27%, absolute neutrophil count(ANC) < 1,500, platelet count < 100,000, serum glutamate oxaloacetate transaminase(SGOT) or serum glutamate pyruvate transaminase (SGPT) > two times normal for age, bilirubin > two times normal for age, alkaline phosphatase > two times normal for age, epidermal growth factor receptor (eGFR) < 30, or evidence of renal failure, hypercholesterolemia. Participants who have medical contraindications to undergoing an MRI will be excluded. Participants with devices implanted in the brain will be excluded. Pregnant participants will be excluded. All young ladies of child bearing potential will have a blood test for pregnancy prior to the start of the study and every study visit for the duration of the study. Participants who have a history of herpes simplex virus, cytomegalovirus, and/or HIV infection will be excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tanjala Gipson, MD
Organizational Affiliation
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19506736
Citation
Napolioni V, Curatolo P. Genetics and molecular biology of tuberous sclerosis complex. Curr Genomics. 2008 Nov;9(7):475-87. doi: 10.2174/138920208786241243.
Results Reference
background
Citation
Gomez M, Sampson JR, Whittemore VH, editors. Tuberous sclerosis complex. 3rd ed. Oxford University Press; 1999.
Results Reference
background
PubMed Identifier
2039137
Citation
Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann N Y Acad Sci. 1991;615:125-7. doi: 10.1111/j.1749-6632.1991.tb37754.x. No abstract available.
Results Reference
background
PubMed Identifier
16359466
Citation
Cross JH. Neurocutaneous syndromes and epilepsy-issues in diagnosis and management. Epilepsia. 2005;46 Suppl 10:17-23. doi: 10.1111/j.1528-1167.2005.00353.x.
Results Reference
background
PubMed Identifier
15921233
Citation
Curatolo P, Bombardieri R, Verdecchia M, Seri S. Intractable seizures in tuberous sclerosis complex: from molecular pathogenesis to the rationale for treatment. J Child Neurol. 2005 Apr;20(4):318-25. doi: 10.1177/08830738050200040901.
Results Reference
background
PubMed Identifier
12622312
Citation
Joinson C, O'Callaghan FJ, Osborne JP, Martyn C, Harris T, Bolton PF. Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med. 2003 Feb;33(2):335-44. doi: 10.1017/s0033291702007092.
Results Reference
background
PubMed Identifier
20643380
Citation
de Vries PJ. Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex. Neurotherapeutics. 2010 Jul;7(3):275-82. doi: 10.1016/j.nurt.2010.05.001.
Results Reference
background
PubMed Identifier
9813776
Citation
Smalley SL. Autism and tuberous sclerosis. J Autism Dev Disord. 1998 Oct;28(5):407-14. doi: 10.1023/a:1026052421693.
Results Reference
background
PubMed Identifier
12023313
Citation
Bolton PF, Park RJ, Higgins JN, Griffiths PD, Pickles A. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain. 2002 Jun;125(Pt 6):1247-55. doi: 10.1093/brain/awf124.
Results Reference
background
Citation
Prescibing Information for Sirolimus. 1999).
Results Reference
background
PubMed Identifier
12742479
Citation
Sindhi R. Sirolimus in pediatric transplant recipients. Transplant Proc. 2003 May;35(3 Suppl):113S-114S. doi: 10.1016/s0041-1345(03)00223-9.
Results Reference
background
PubMed Identifier
18568033
Citation
Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, Kwiatkowski DJ, Ramesh V, Silva AJ. Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Nat Med. 2008 Aug;14(8):843-8. doi: 10.1038/nm1788. Epub 2008 Jun 22.
Results Reference
background
PubMed Identifier
18389497
Citation
Zeng LH, Xu L, Gutmann DH, Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol. 2008 Apr;63(4):444-53. doi: 10.1002/ana.21331.
Results Reference
background
PubMed Identifier
16453317
Citation
Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G, Dinopoulos A, Thomas G, Crone KR. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006 Mar;59(3):490-8. doi: 10.1002/ana.20784.
Results Reference
background
PubMed Identifier
21047224
Citation
Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010 Nov 4;363(19):1801-11. doi: 10.1056/NEJMoa1001671.
Results Reference
background
PubMed Identifier
21525172
Citation
Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, Sampson JR. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.1158/1078-0432.CCR-11-0445. Epub 2011 Apr 27.
Results Reference
background
PubMed Identifier
18495876
Citation
Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, Kwiatkowski DJ. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008 May 21;28(21):5422-32. doi: 10.1523/JNEUROSCI.0955-08.2008.
Results Reference
background
PubMed Identifier
21410393
Citation
McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16.
Results Reference
background
PubMed Identifier
20823888
Citation
Flaig TW, Costa LJ, Gustafson DL, Breaker K, Schultz MK, Crighton F, Kim FJ, Drabkin H. Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib. Br J Cancer. 2010 Sep 7;103(6):796-801. doi: 10.1038/sj.bjc.6605868.
Results Reference
background
PubMed Identifier
20815021
Citation
Asrani SK, Leise MD, West CP, Murad MH, Pedersen RA, Erwin PJ, Tian J, Wiesner RH, Kim WR. Use of sirolimus in liver transplant recipients with renal insufficiency: a systematic review and meta-analysis. Hepatology. 2010 Oct;52(4):1360-70. doi: 10.1002/hep.23835.
Results Reference
background
PubMed Identifier
20501622
Citation
Armstrong AJ, Netto GJ, Rudek MA, Halabi S, Wood DP, Creel PA, Mundy K, Davis SL, Wang T, Albadine R, Schultz L, Partin AW, Jimeno A, Fedor H, Febbo PG, George DJ, Gurganus R, De Marzo AM, Carducci MA. A pharmacodynamic study of rapamycin in men with intermediate- to high-risk localized prostate cancer. Clin Cancer Res. 2010 Jun 1;16(11):3057-66. doi: 10.1158/1078-0432.CCR-10-0124. Epub 2010 May 25.
Results Reference
background
PubMed Identifier
20687497
Citation
Habib SL. Tuberous sclerosis complex and DNA repair. Adv Exp Med Biol. 2010;685:84-94. doi: 10.1007/978-1-4419-6448-9_8.
Results Reference
background
Citation
Rapamune: U.S. Physician Prescribing Information. 1999).
Results Reference
background
PubMed Identifier
19060543
Citation
Krams SM, Martinez OM. Epstein-Barr virus, rapamycin, and host immune responses. Curr Opin Organ Transplant. 2008 Dec;13(6):563-8. doi: 10.1097/MOT.0b013e3283186ba9.
Results Reference
background
PubMed Identifier
2516000
Citation
Novak M, Guest C. Application of a multidimensional caregiver burden inventory. Gerontologist. 1989 Dec;29(6):798-803. doi: 10.1093/geront/29.6.798.
Results Reference
background
Citation
Abidin R. Parental stress index - 4, short form. fourth edition ed. Odessa, FL: Psychological Assessment Resources, Inc.; 2009.
Results Reference
background
PubMed Identifier
18703161
Citation
Staley BA, Montenegro MA, Major P, Muzykewicz DA, Halpern EF, Kopp CM, Newberry P, Thiele EA. Self-injurious behavior and tuberous sclerosis complex: frequency and possible associations in a population of 257 patients. Epilepsy Behav. 2008 Nov;13(4):650-3. doi: 10.1016/j.yebeh.2008.07.010. Epub 2008 Aug 30.
Results Reference
background
Citation
Seizuretracker.com [Internet].; 2012.
Results Reference
background
PubMed Identifier
10385849
Citation
Roach ES, DiMario FJ, Kandt RS, Northrup H. Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol. 1999 Jun;14(6):401-7. doi: 10.1177/088307389901400610.
Results Reference
background
PubMed Identifier
15155396
Citation
O'Callaghan FJ, Harris T, Joinson C, Bolton P, Noakes M, Presdee D, Renowden S, Shiell A, Martyn CN, Osborne JP. The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex. Arch Dis Child. 2004 Jun;89(6):530-3. doi: 10.1136/adc.2003.026815.
Results Reference
background
PubMed Identifier
11591847
Citation
Asano E, Chugani DC, Muzik O, Behen M, Janisse J, Rothermel R, Mangner TJ, Chakraborty PK, Chugani HT. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology. 2001 Oct 9;57(7):1269-77. doi: 10.1212/wnl.57.7.1269.
Results Reference
background
PubMed Identifier
16417883
Citation
Doherty C, Goh S, Young Poussaint T, Erdag N, Thiele EA. Prognostic significance of tuber count and location in tuberous sclerosis complex. J Child Neurol. 2005 Oct;20(10):837-41. doi: 10.1177/08830738050200101301.
Results Reference
background
PubMed Identifier
17335641
Citation
Raznahan A, Higgins NP, Griffiths PD, Humphrey A, Yates JR, Bolton PF. Biological markers of intellectual disability in tuberous sclerosis. Psychol Med. 2007 Sep;37(9):1293-304. doi: 10.1017/S0033291707000177. Epub 2007 Mar 5.
Results Reference
background
Citation
Roid G, Miller L. Leiter international performance scale, revised. Torrance, CA: Western Psychological Services; 1998.
Results Reference
background
Citation
Mullen E. Mullen scales of early learning. Circle Pines, MN: American Guidance Service, Inc.; 1995.
Results Reference
background
PubMed Identifier
7525138
Citation
Wachtel RC, Shapiro BK, Palmer FB, Allen MC, Capute AJ. CAT/CLAMS. A tool for the pediatric evaluation of infants and young children with developmental delay. Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale. Clin Pediatr (Phila). 1994 Jul;33(7):410-5. doi: 10.1177/000992289403300706.
Results Reference
background
PubMed Identifier
2335488
Citation
Iwata BA, Pace GM, Kissel RC, Nau PA, Farber JM. The Self-Injury Trauma (SIT) Scale: a method for quantifying surface tissue damage caused by self-injurious behavior. J Appl Behav Anal. 1990 Spring;23(1):99-110. doi: 10.1901/jaba.1990.23-99.
Results Reference
background
PubMed Identifier
11055457
Citation
Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, Pickles A, Rutter M. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000 Jun;30(3):205-23.
Results Reference
background
PubMed Identifier
7814313
Citation
Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994 Oct;24(5):659-85. doi: 10.1007/BF02172145.
Results Reference
background
Citation
Constantino J. The social responsiveness scale. Los Angeles: Western Psychological Services; 2002.
Results Reference
background
Citation
Rutter M, Bailey A, Lord C. Social communication questionnaire. Western Psychological Services; 2003.
Results Reference
background
PubMed Identifier
20554253
Citation
Granader YE, Bender HA, Zemon V, Rathi S, Nass R, Macallister WS. The clinical utility of the Social Responsiveness Scale and Social Communication Questionnaire in tuberous sclerosis complex. Epilepsy Behav. 2010 Jul;18(3):262-6. doi: 10.1016/j.yebeh.2010.04.010.
Results Reference
background
PubMed Identifier
20405194
Citation
Mirenda P, Smith IM, Vaillancourt T, Georgiades S, Duku E, Szatmari P, Bryson S, Fombonne E, Roberts W, Volden J, Waddell C, Zwaigenbaum L; Pathways in ASD Study Team. Validating the Repetitive Behavior Scale-revised in young children with autism spectrum disorder. J Autism Dev Disord. 2010 Dec;40(12):1521-30. doi: 10.1007/s10803-010-1012-0.
Results Reference
background
PubMed Identifier
6630801
Citation
Kazdin AE. Single-case research designs in clinical child psychiatry. J Am Acad Child Psychiatry. 1983 Sep;22(5):423-32. doi: 10.1016/s0002-7138(09)61503-x. No abstract available.
Results Reference
background
PubMed Identifier
19144108
Citation
Sanchez CP, He YZ. Bone growth during rapamycin therapy in young rats. BMC Pediatr. 2009 Jan 13;9:3. doi: 10.1186/1471-2431-9-3.
Results Reference
background
PubMed Identifier
17370095
Citation
Alvarez-Garcia O, Carbajo-Perez E, Garcia E, Gil H, Molinos I, Rodriguez J, Ordonez FA, Santos F. Rapamycin retards growth and causes marked alterations in the growth plate of young rats. Pediatr Nephrol. 2007 Jul;22(7):954-61. doi: 10.1007/s00467-007-0456-8. Epub 2007 Mar 17.
Results Reference
background
PubMed Identifier
19495804
Citation
Rangel GA, Ariceta G. Growth failure associated with sirolimus: case report. Pediatr Nephrol. 2009 Oct;24(10):2047-50. doi: 10.1007/s00467-009-1215-9. Epub 2009 Jun 3.
Results Reference
background
Links:
URL
http://www.kennedykrieger.org/research-training/participate-in-research/clinical-trials
Description
Kennedy Krieger Institute Clinical Trials Unit
URL
http://www.kennedykrieger.org/patient-care/patient-care-programs/outpatient-programs/tuberous-sclerosis-clinic
Description
TSC clinic at Kennedy Krieger Institute

Learn more about this trial

Rapalogues for Autism Phenotype in TSC: A Feasibility Study

We'll reach out to this number within 24 hrs