DS-Riv: Rivastigmine Study in Adolescents With Down Syndrome
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| 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:
|
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kennedy Krieger Institute | Baltimore | Maryland | United States | 21205 |
| 2 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Duke University
- 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00013682
Study Results
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 Detail | 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. |
| Arm/Group Title | Rivastigmine- Liquid Form | Liquid Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: 12 Week | ||
| STARTED | 4 | 4 |
| COMPLETED | 4 | 4 |
| NOT COMPLETED | 0 | 0 |
| Period Title: 12 Week | ||
| STARTED | 12 | 11 |
| COMPLETED | 12 | 10 |
| NOT COMPLETED | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | 20 Week Rivastigmine- Liquid Form | 20 Week Liquid Placebo | 12 Week Rivastigmine- Liquid Form | 12 Week Liquid Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 12 | 11 | 4 | 4 | 31 |
| Age (Count of Participants) | |||||
| <=18 years |
12
100%
|
11
100%
|
4
100%
|
4
100%
|
31
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
8
66.7%
|
6
54.5%
|
2
50%
|
2
50%
|
18
58.1%
|
| Male |
4
33.3%
|
5
45.5%
|
2
50%
|
2
50%
|
13
41.9%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
12
100%
|
11
100%
|
4
100%
|
4
100%
|
31
100%
|
Outcome Measures
| Title | Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who completed the 20 week period were included in analysis except for 2 subjects whose form was completed incorrectly. |
| Arm/Group Title | Rivastigmine- Liquid Form | Liquid Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 10 | 10 |
| Mean (Standard Deviation) [units on a scale] |
-1.7
(3.2)
|
2.0
(3.6)
|
| Title | Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who completed the 20 week period were included in analysis except for 1 subjects whose form was completed incorrectly. |
| Arm/Group Title | Rivastigmine- Liquid Form | Liquid Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 11 | 10 |
| Mean (Standard Deviation) [units on a scale] |
-3.6
(7.7)
|
-6.1
(12.0)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | 20 Week: Rivastigmine- Liquid Form | 20 Week: Liquid Placebo | 12 Week: Rivastigmine- Liquid Form | 12 Week: Liquid Placebo | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| 20 Week: Rivastigmine- Liquid Form | 20 Week: Liquid Placebo | 12 Week: Rivastigmine- Liquid Form | 12 Week: Liquid Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| 20 Week: Rivastigmine- Liquid Form | 20 Week: Liquid Placebo | 12 Week: Rivastigmine- Liquid Form | 12 Week: Liquid Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| 20 Week: Rivastigmine- Liquid Form | 20 Week: Liquid Placebo | 12 Week: Rivastigmine- Liquid Form | 12 Week: Liquid Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/12 (91.7%) | 8/11 (72.7%) | 3/4 (75%) | 4/4 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lumps in neck | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Eye disorders | ||||||||
| Eye twitch | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhea | 3/12 (25%) | 2/11 (18.2%) | 0/4 (0%) | 3/4 (75%) | ||||
| Nausea | 3/12 (25%) | 3/11 (27.3%) | 1/4 (25%) | 1/4 (25%) | ||||
| Stomach ache | 5/12 (41.7%) | 3/11 (27.3%) | 0/4 (0%) | 1/4 (25%) | ||||
| Vomiting | 3/12 (25%) | 1/11 (9.1%) | 1/4 (25%) | 2/4 (50%) | ||||
| Indigestion | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Constipation | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Sleepy | 2/12 (16.7%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| excessive gas | 0/12 (0%) | 0/11 (0%) | 1/4 (25%) | 0/4 (0%) | ||||
| General disorders | ||||||||
| Cold | 3/12 (25%) | 2/11 (18.2%) | 0/4 (0%) | 0/4 (0%) | ||||
| Stomach flu | 2/12 (16.7%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Fever | 0/12 (0%) | 2/11 (18.2%) | 0/4 (0%) | 0/4 (0%) | ||||
| Fatigue | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Increased bilirubin | 0/12 (0%) | 1/11 (9.1%) | 0/4 (0%) | 0/4 (0%) | ||||
| Infections and infestations | ||||||||
| Vaginal yeast infection | 0/12 (0%) | 1/11 (9.1%) | 0/4 (0%) | 0/4 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Cut | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/12 (8.3%) | 1/11 (9.1%) | 1/4 (25%) | 1/4 (25%) | ||||
| Weight gain | 0/12 (0%) | 1/11 (9.1%) | 0/4 (0%) | 0/4 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Weakness | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Leg cramps | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 2/4 (50%) | ||||
| Headache | 1/12 (8.3%) | 1/11 (9.1%) | 1/4 (25%) | 0/4 (0%) | ||||
| Trouble sleeping | 1/12 (8.3%) | 1/11 (9.1%) | 0/4 (0%) | 2/4 (50%) | ||||
| Shakiness | 0/12 (0%) | 1/11 (9.1%) | 0/4 (0%) | 0/4 (0%) | ||||
| Restless legs | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Foot twitching | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Fainted | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Psychiatric disorders | ||||||||
| Assertive, stubborn, more emotional | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| behavior problems | 0/12 (0%) | 0/11 (0%) | 3/4 (75%) | 1/4 (25%) | ||||
| nightmares | 0/12 (0%) | 0/11 (0%) | 1/4 (25%) | 0/4 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Incontinence | 1/12 (8.3%) | 1/11 (9.1%) | 0/4 (0%) | 0/4 (0%) | ||||
| Frequent urination | 0/12 (0%) | 1/11 (9.1%) | 1/4 (25%) | 0/4 (0%) | ||||
| Urinary track infection | 0/12 (0%) | 1/11 (9.1%) | 0/4 (0%) | 0/4 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Menstural cramps | 2/12 (16.7%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Nasal congestion | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Boil | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Pale coloring | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Itchy | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Rash | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Worsening acne | 1/12 (8.3%) | 0/11 (0%) | 0/4 (0%) | 0/4 (0%) | ||||
| Worsening alopecia | 0/12 (0%) | 1/11 (9.1%) | 0/4 (0%) | 0/4 (0%) | ||||
| acne | 0/12 (0%) | 0/11 (0%) | 0/4 (0%) | 1/4 (25%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jane Ann Baker,MS, CGC |
|---|---|
| Organization | Duke University Medical Center |
| Phone | 919-668-4576 |
| janeann.mckillop@duke.edu |
- Pro00013682