Down Syndrome
Conditions
Keywords
Clinical trial, Down syndrome, adolescents, cognitive, rivastigmine
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.
Interventions
DRUGRivastigmine
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.
OTHERLiquid 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.
Sponsors
Taishoff Family Foundation
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) | 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. |
Countries
United States
Participant flow
Recruitment details
8 participant started and completed the 12 week period. The protocol was amended and 23 subject enrolled into the 20 week amended period (22 completed).
Pre-assignment details
42 subjects signed consent, 10 were screen failures, 1 withdrew consent prior to being assigned to an arm, 1 was withdrawn by PI after being assigned an arm for noncompliance, 30 completed study.
Participants by arm
| Arm | Count |
|---|---|
| 20 Week 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. | 12 |
| 20 Week 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.
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. | 11 |
| 12 Week 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 four weeks. At the week 6 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 6 weeks. | 4 |
| 12 Week 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.
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. | 4 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 20 Week | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | 12 Week Rivastigmine- Liquid Form | 20 Week Rivastigmine- Liquid Form | 20 Week Liquid Placebo | 12 Week Liquid Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 12 Participants | 11 Participants | 4 Participants | 31 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 4 participants | 12 participants | 11 participants | 4 participants | 31 participants |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 6 Participants | 2 Participants | 18 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 5 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 12 | 8 / 11 | 3 / 4 | 4 / 4 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 0 / 4 | 0 / 4 |
Outcome results
Primary
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.
Time frame: Baseline & Study termination (Week 20)
Population: All subjects who completed the 20 week period were included in analysis except for 2 subjects whose form was completed incorrectly.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivastigmine- Liquid Form | Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) | -1.7 units on a scale | Standard Deviation 3.2 |
| Liquid Placebo | Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) | 2.0 units on a scale | Standard Deviation 3.6 |
Secondary
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.
Time frame: Baseline and Final (Week 20) visit
Population: All subjects who completed the 20 week period were included in analysis except for 1 subjects whose form was completed incorrectly.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivastigmine- Liquid Form | Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) | -3.6 units on a scale | Standard Deviation 7.7 |
| Liquid Placebo | Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) | -6.1 units on a scale | Standard Deviation 12 |