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

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

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.

Study Overview

• Status: Completed
• Conditions: Down Syndrome
• Intervention / Treatment: Drug: Rivastigmine; Other: Liquid Placebo

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
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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 Names: Rivastigmine-Excelon
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form)	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.	Baseline & Study termination (Week 20)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P)	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.	Baseline and Final (Week 20) visit

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.; Taishoff Family Foundation
• Investigators: Principal Investigator: George Capone, MD, Kennedy Krieger Institute/Johns Hopkins

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: March 8, 2010
• First Submitted That Met QC Criteria: March 9, 2010
• First Posted (Estimate): March 10, 2010

Study Record Updates

• Last Update Posted (Estimate): April 6, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: adolescents; Clinical trial; Down syndrome; cognitive; rivastigmine
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Down Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Rivastigmine
• Other Study ID Numbers: Pro00013682