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| Name | Class |
|---|---|
| Taishoff Family Foundation | UNKNOWN |
| Hugo W. Moser Research Institute at Kennedy Krieger, Inc. | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rivastigmine- Liquid form | Experimental | 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 | Placebo Comparator | Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rivastigmine | Drug | 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. |
| 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) |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Priya Kishnani, MD | Duke University | Principal Investigator |
| George Capone, MD | Kennedy Krieger Institute/Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States | ||
| Duke University Medical Center |
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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 12 Week |
| |||||||||||||
| 20 Week |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All subjects who completed the 20 week period were included in analysis except for 2 subjects whose form was completed incorrectly. | Posted | Mean | Standard Deviation | units on a scale | Baseline & Study termination (Week 20) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jane Ann Baker,MS, CGC | Duke University Medical Center | 919-668-4576 | janeann.mckillop@duke.edu |
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| ID | Term |
|---|---|
| D004314 | Down Syndrome |
| ID | Term |
|---|---|
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000068836 | Rivastigmine |
| ID | Term |
|---|---|
| D048448 | Phenylcarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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|
|
| Liquid Placebo | Other | Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste. |
|
| Baseline and Final (Week 20) visit |
| Durham |
| North Carolina |
| 27710 |
| United States |
| NOT COMPLETED |
|
|
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
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.
| OG001 | 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. |
|
|
| 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. | All subjects who completed the 20 week period were included in analysis except for 1 subjects whose form was completed incorrectly. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Final (Week 20) visit |
|
|
|
| 0 |
| 12 |
| 11 |
| 12 |
| EG001 | 20 Week: Liquid Placebo | 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. | 0 | 11 | 8 | 11 |
| EG002 | 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. | 0 | 4 | 3 | 4 |
| EG003 | 12 Week: Liquid Placebo | 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. | 0 | 4 | 4 | 4 |
| Nausea | Gastrointestinal disorders |
|
| Stomach ache | Gastrointestinal disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Dizziness | Nervous system disorders |
|
| Headache | Nervous system disorders |
|
| Trouble sleeping | Nervous system disorders |
|
| Decreased appetite | Metabolism and nutrition disorders |
|
| Shakiness | Nervous system disorders |
|
| Weakness | Musculoskeletal and connective tissue disorders |
|
| Lumps in neck | Blood and lymphatic system disorders |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders |
|
| Boil | Skin and subcutaneous tissue disorders |
|
| Menstural cramps | Reproductive system and breast disorders |
|
| Cut | Injury, poisoning and procedural complications |
|
| Restless legs | Nervous system disorders |
|
| Pale coloring | Skin and subcutaneous tissue disorders |
|
| Foot twitching | Nervous system disorders |
|
| Itchy | Skin and subcutaneous tissue disorders |
|
| Eye twitch | Eye disorders |
|
| Rash | Skin and subcutaneous tissue disorders |
|
| Increased bilirubin | Hepatobiliary disorders |
|
| Indigestion | Gastrointestinal disorders |
|
| Constipation | Gastrointestinal disorders |
|
| Worsening acne | Skin and subcutaneous tissue disorders |
|
| Cold | General disorders |
|
| Stomach flu | General disorders |
|
| Fever | General disorders |
|
| Worsening alopecia | Skin and subcutaneous tissue disorders |
|
| Leg cramps | Musculoskeletal and connective tissue disorders |
|
| Incontinence | Renal and urinary disorders |
|
| Assertive, stubborn, more emotional | Psychiatric disorders |
|
| Fainted | Nervous system disorders |
|
| Sleepy | Gastrointestinal disorders |
|
| Fatigue | General disorders |
|
| Frequent urination | Renal and urinary disorders |
|
| Weight gain | Metabolism and nutrition disorders |
|
| excessive gas | Gastrointestinal disorders |
|
| behavior problems | Psychiatric disorders |
|
| Vaginal yeast infection | Infections and infestations |
|
| Urinary track infection | Renal and urinary disorders |
|
| nightmares | Psychiatric disorders |
|
| acne | Skin and subcutaneous tissue disorders |
|
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| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009930 |
| Organic Chemicals |