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

• ClinicalTrials.gov Identifier: NCT01084135
• Recruitment Status: Completed
• First Posted: March 10, 2010
• Results First Posted: March 12, 2015
• Last Update Posted: April 6, 2015
• Sponsor: Duke University
• Collaborators: Taishoff Family Foundation; Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• Information provided by (Responsible Party): Duke University

Tracking Information

• First Submitted Date: March 8, 2010
• First Posted Date: 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: November 2009
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Rivastigmine Study in Adolescents With Down Syndrome
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Down Syndrome

Intervention

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 6, 2014): 42
• Original Estimated Enrollment (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

Inclusion Criteria:

1. Correct VERBAL responses for 7/9 of the Expressive One Word Picture Vocabulary Test items.
2. Subject able to put at least 2-3 words together in conversational speech.
3. Subject's speech is understandable to the examiner for the majority of the time.
4. Subjects are in good health and medically stable

Exclusion Criteria:

1. Subject uses sign language as a primary means of communication
2. 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: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01084135
• Other Study ID Numbers: Pro00013682
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Duke University
• Study Sponsor: Duke University

Collaborators

• Taishoff Family Foundation
• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Investigators

• 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