Rivastigmine Study in Adolescents With Down Syndrome (DS-Riv)

Tracking Information
First Submitted Date ICMJE	March 8, 2010
First Posted Date ICMJE	March 10, 2010
Results First Submitted Date	February 27, 2015
Results First Posted Date	March 12, 2015
Last Update Posted Date	April 6, 2015
Study Start Date ICMJE	November 2009
Actual Primary Completion Date	February 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 27, 2015)	Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) [ Time Frame: Baseline & Study termination (Week 20) ]; The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. In this study, the change between each subject's ABC at Baseline and the Final Visit was computed. A rise in standard scores from Baseline to the Final Visit indicates improvement.
Original Primary Outcome Measures ICMJE; (submitted: March 9, 2010)	Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) [ Time Frame: Baseline & Study termination (Week 20) ]; Indirect (parent report) measure of adaptive function
Change History	Complete list of historical versions of study NCT01084135 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 27, 2015)	Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) [ Time Frame: Baseline and Final (Week 20) visit ]; The Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) is a parent report measure of executive function behaviors in children in their home setting. It yields an overall score (Global Executive Composite, GEC) that is based on its five clinical scales. Raw scores range from 63 to 189. Higher scores suggest that an individual's executive function skills are more problematic. In this study, the change between each subject's raw score at Baseline and the Final Visit was computed for the Global Executive Composite. A decline in raw scores from Baseline to the Final Visit indicates improvement.
Original Secondary Outcome Measures ICMJE; (submitted: March 9, 2010)	Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) [ Time Frame: Baseline and Final (Week 20) visit ]; Indirect measure of executive function
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Rivastigmine Study in Adolescents With Down Syndrome
Official Title ICMJE	A 20-Week Double-Blind Placebo Controlled Clinical Trial to Evaluate the Safety and Efficacy of Rivastigmine in Children (Ages 10-18) With Down Syndrome
Brief Summary	The purpose of this study is to determine if short term use of rivastigmine can improve functional abilities (for example, language, memory, and executive function) in adolescents with Down syndrome.
Detailed Description	This 24 week, double-blind, placebo controlled trial will be completed at the Clinical Research Unit of Duke University Medical Center and at the Kennedy Krieger Institute (KKI). Sixteen evaluable subjects will be enrolled at Duke and 24 evaluable subjects will be enrolled at KKI. The study consists of four visits, a screening visit (-4 weeks), a baseline visit (week 0); a safety visit at week 10, and a final/termination visit at week 20. The specific aims of this study are to: a) investigate efficacy of rivastigmine tartrate treatment; b) build upon our open-label treatment results of overall function and language improvement in adolescents with Down syndrome (DS) in a double-blind, placebo-controlled clinical trial; and c) investigate other specific cognitive domains that may selectively respond to rivastigmine tartrate treatment. The original IRB-approved protocol included the Parent/Caregiver Rating Form of the Vineland Adaptive Behavior Scales- Second Edition (VABS-II) . The protocol was amended to replace the Parent/Caregiver Rating Form of the Vineland Adaptive Behavior Scales- Second Edition (VABS-II) with the Vineland Adaptive Behavior Scales, Second Edition, Survey Interview Form. The protocol was also amended to extend the trial from 12 weeks to 20 weeks. Due to the changes in the amended protocol the subject enrolled prior to the IRB amendment will not be included in the data analysis section.
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Down Syndrome
Intervention ICMJE	Drug: Rivastigmine At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. Subjects receiving placebo will maintain the same schedule. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study. Other Name: Rivastigmine-Excelon; Other: Liquid Placebo Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Study Arms	Experimental: Rivastigmine- Liquid form At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study. Intervention: Drug: Rivastigmine; Placebo Comparator: Liquid placebo Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste. Intervention: Other: Liquid Placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 6, 2014)	42
Original Estimated Enrollment ICMJE; (submitted: March 9, 2010)	40
Actual Study Completion Date	February 2014
Actual Primary Completion Date	February 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Correct VERBAL responses for 7/9 of the Expressive One Word Picture Vocabulary Test items.; Subject able to put at least 2-3 words together in conversational speech.; Subject's speech is understandable to the examiner for the majority of the time.; Subjects are in good health and medically stable Exclusion Criteria: Subject uses sign language as a primary means of communication; Subject has a medical history that contraindicate the use of rivastigmine (For example, patients with active seizure disorders, asthma, celiac disease, heart disease or heart rhythm disorders).
Sex/Gender	Sexes Eligible for Study: All
Ages	10 Years to 17 Years (Child)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01084135
Other Study ID Numbers ICMJE	Pro00013682
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Duke University
Study Sponsor ICMJE	Duke University
Collaborators ICMJE	Taishoff Family Foundation; Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Investigators ICMJE	Principal Investigator: Priya Kishnani, MD Duke University Principal Investigator: George Capone, MD Kennedy Krieger Institute/Johns Hopkins
PRS Account	Duke University
Verification Date	February 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP