Mild Cognitive Impairment in Parkinson's Disease
Study Details
Study Description
Brief Summary
Mild cognitive impairment, including difficulty with solving problems, planning, attention, or recalling information, can be a significant problem for individuals with Parkinson's disease. Even mild cognitive difficulties can lead to worse functioning, quality of life, depression, and difficulty for caregivers. Thus, ideally treatment at this stage would improve both cognitive symptoms and some of the other problems associated with these symptoms.
Despite the fact that mild cognitive impairment is a serious problem for Parkinson's disease patients little is known about how best to treat it. This study is a 24-week clinical trial to see if a Food and Drug Administration (FDA)-approved drug, the Exelon (rivastigmine) Patch, is useful in treating mild cognitive impairment in patients with Parkinson's disease. Currently, the Exelon (rivastigmine) Patch is FDA-approved for the treatment of mild to moderate dementia in Alzheimer and Parkinson's disease patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
This study has 2 phases. Each phase will last 10 weeks and there will be a 4-week break between the 2 phases. Thus, you will be enrolled in the study for a total of 24 weeks. Over the course of the 24-week period we will schedule to see you in-person 6 times and check-in with you on the telephone 4 times, 2 times during each phase.
Phase I
Screening (may be the same day as the baseline visit) - Research personnel will determine if you are eligible to participate in this study.
Visit 1 - Baseline Visit, Start Study Medication
Phone Call 1 - Check in to see how you are feeling after starting the study medication
Visit 2 - 4 Weeks after Baseline, Increase Study Medication if tolerated
Phone Call 2 - Check in to see how you are feeling after increasing the study medication
Visit 3/ Phase I Termination Visit - 10 Weeks after Baseline (Phase I Termination Visit)
4 Week Break (no study medication)
Phase II
Visit 4/ Phase II Baseline - 14 Weeks after Baseline, Start Study Medication
Phone Call 3 - Check in to see how you are feeling after starting the study medication
Visit 5 - 18 Weeks after Baseline, Increase Study Medication
Phone Call 4 - Check in to see how you are feeling after increasing the study medication
Visit 6/Phase II and Study Termination Visit - 24 Weeks after Baseline
Visits 1, 3, 4, and 6 will last for about 2 ½ hours and visits 2 and 5 about 30 minutes. The 'check in' phone calls will last approximately 5-10 minutes.
After 24 weeks, your study participation will be over.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Patch
|
Drug: Placebo Patches
The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine).
|
| Active Comparator: Exelon Patch (rivastigmine transdermal system)
|
Drug: Exelon Patch (rivastigmine transdermal system)
The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia.
5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours )
|
Outcome Measures
Primary Outcome Measures
- Alzheimer's Disease Cooperative Study- Clinical Global Impression Change (ADCS-CGIC) [The ADCS-CGIC will be administered at the end of each study phase.]
The ADCS-CGIC is the most commonly used measure of global change in dementia psychopharmacology studies. This assessment is a measure of change, thus it is not appropriate for baseline administration and only administered at the end of phase visit. The scale rates total improvement on a 7 point scale: = Very much improved = Much improved = Minimally improved = No change = Minimally worse = Much worse = Very much worse A participant scoring a 1 or 2 is considered a responder on the CGI scale.
Secondary Outcome Measures
- Montreal Cognitive Assessment (MoCA) [The MoCA was administered in the beginning and end of each study phase.]
The MoCA will be used as the global cognitive screening instrument. It will also be administered in the clinical trial at baseline and the final visits of each phase as a secondary outcome measure of global cognition. Scores on the MoCA range from 0-30 with 26-30 indicating normal global cognition.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants must be experiencing symptoms of mild cognitive impairment; this will be determined by study personnel.
-
Participants must be on a sable medication regimen for 2 months prior to starting the study (necessary dose adjustments during the study are acceptable).
-
Participants are capable of giving informed consent supported by not meeting Parkinson's disease Dementia criteria; this will be determined by study personnel.
Exclusion Criteria:
-
Active suicide ideation.
-
Weighing less than 100 lbs (45 kgs).
-
History of Deep Brain Stimulation surgery.
-
Diagnosis of Dementia
-
Taking certain types of medications may be an exclusion criteria, this will be reviewed with all potential participants.
-
Females that are pregnant, planning to become pregnant, or are breastfeeding will not be included in the study. Females of childbearing potential will need to verify that they are not pregnant by a negative urine pregnancy test.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania, Ralston House | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
Investigators
- Principal Investigator: Daniel Weintraub, MD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 813803
Study Results
Participant Flow
| Recruitment Details | Potential participants were a convenience sample of PD patients primarily from the Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania. Patients between the ages of 40 and 85 y with idiopathic PD for more than 2 years and reporting cognitive were screened for study participation. |
|---|---|
| Pre-assignment Detail | 48 participants assessed for eligibility, 28 randomized (17 did not meet inclusion/exclusion criteria and 3 refused to participate after screening) |
| Arm/Group Title | Placebo First Then Rivastigmine | Rivastigmine First Then Placebo |
|---|---|---|
| Arm/Group Description | Placebo patches placed on skin daily in Phase 1 and Rivastigmine 5-10cm2 patches in Phase 2. Each phase lasted for 10 weeks. Exelon Patch (rivastigmine transdermal system): The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia. 5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours ) Placebo Patches: The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine). | 5-10cm2 rivastigmine patch daily first in phase 1 and placebo patch daily in phase 2. Each phase lasted for 10 weeks. Exelon Patch (rivastigmine transdermal system): The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia. 5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours ) Placebo Patches: The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine). |
| Period Title: Phase 1 | ||
| STARTED | 14 | 14 |
| COMPLETED | 14 | 13 |
| NOT COMPLETED | 0 | 1 |
| Period Title: Phase 1 | ||
| STARTED | 12 | 14 |
| COMPLETED | 12 | 14 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo Patch First Then 5-10cm2 Rivastigmine Patch | 5-10cm2 Rivastigmine Patch First First Then Placebo Patch | Total |
|---|---|---|---|
| Arm/Group Description | Placebo Patches: The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine). Exelon Patch (rivastigmine transdermal system): The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia. 5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours ) Each phase lasted 10 weeks. | Exelon Patch (rivastigmine transdermal system): The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia. 5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours ) Placebo Patches: The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine). Each phase lasted 10 weeks. | Total of all reporting groups |
| Overall Participants | 14 | 14 | 28 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
66.1
(5.5)
|
62.6
(10.1)
|
64.3
(8.2)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
14.3%
|
4
28.6%
|
6
21.4%
|
| Male |
12
85.7%
|
10
71.4%
|
22
78.6%
|
Outcome Measures
| Title | Alzheimer's Disease Cooperative Study- Clinical Global Impression Change (ADCS-CGIC) |
|---|---|
| Description | The ADCS-CGIC is the most commonly used measure of global change in dementia psychopharmacology studies. This assessment is a measure of change, thus it is not appropriate for baseline administration and only administered at the end of phase visit. The scale rates total improvement on a 7 point scale: = Very much improved = Much improved = Minimally improved = No change = Minimally worse = Much worse = Very much worse A participant scoring a 1 or 2 is considered a responder on the CGI scale. |
| Time Frame | The ADCS-CGIC will be administered at the end of each study phase. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Please note this study utilized the crossover design (i.e. participants were exposed to two phases of treatment, one with placebo and one with Exelon patch). The data are comparing differences in treatment groups. Over the course of this study 2 participants discontinued study participation. |
| Arm/Group Title | Placebo Patch | Exelon Patch (Rivastigmine Transdermal System) |
|---|---|---|
| Arm/Group Description | Placebo Patches: The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine). | Exelon Patch (rivastigmine transdermal system): The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia. 5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours ) |
| Measure Participants | 26 | 28 |
| Mean (Standard Deviation) [scores on the CGIC] |
3.92
(0.94)
|
3.48
(0.89)
|
| Title | Montreal Cognitive Assessment (MoCA) |
|---|---|
| Description | The MoCA will be used as the global cognitive screening instrument. It will also be administered in the clinical trial at baseline and the final visits of each phase as a secondary outcome measure of global cognition. Scores on the MoCA range from 0-30 with 26-30 indicating normal global cognition. |
| Time Frame | The MoCA was administered in the beginning and end of each study phase. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Please note this study utilized the crossover design (i.e. participants were exposed to two phases of treatment, one with placebo and one with Exelon patch). The data are comparing differences in treatment groups. |
| Arm/Group Title | Placebo | Rivastigmine |
|---|---|---|
| Arm/Group Description | Placebo Patches: The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine). | Exelon Patch (rivastigmine transdermal system): The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia. 5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours ) |
| Measure Participants | 23 | 23 |
| Baseline |
25.08
(2.7)
|
24.93
(2.5)
|
| Week 16 |
24.73
(3.7)
|
25.6
(2.7)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Patch, Exelon Patch (Rivastigmine Transdermal System) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cohen's D |
| Estimated Value | .35 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Adverse events were recorded at every study visit post baseline (Phase 1: Week 4 and Week 10; Phase 2: Week 14, Week 18 and Week 24). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | We used a modified version of the Treatment Emergent Symptom Scale (TESS) to assess psychiatric, cognitive, and motor adverse effects. | |||
| Arm/Group Title | Placebo Patch | Exelon Patch (Rivastigmine Transdermal System) | ||
| Arm/Group Description | Placebo Patches: The placebo patches will appear identical to the medication patches however they will be inactive (they will not contain rivastigmine). | Exelon Patch (rivastigmine transdermal system): The Exelon Patch (rivastigmine transdermal system) is a Cholinesterase Inhibitor approved by the FDA to treat Alzheimer's and Parkinson's Disease Dementia. 5-10cm2 (4.6-9.5 mg of rivastigmine/24 hours ) | ||
All Cause Mortality |
||||
| Placebo Patch | Exelon Patch (Rivastigmine Transdermal System) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo Patch | Exelon Patch (Rivastigmine Transdermal System) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/26 (0%) | 0/28 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo Patch | Exelon Patch (Rivastigmine Transdermal System) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/26 (34.6%) | 11/28 (39.3%) | ||
| General disorders | ||||
| Pain | 4/26 (15.4%) | 5/28 (17.9%) | ||
| Other | 9/26 (34.6%) | 11/28 (39.3%) | ||
| Fatigue | 2/26 (7.7%) | 4/28 (14.3%) | ||
| Insomnia | 2/26 (7.7%) | 4/28 (14.3%) | ||
| Weight Loss | 3/26 (11.5%) | 1/28 (3.6%) | ||
| Cognitive Impairment | 3/26 (11.5%) | 0/28 (0%) | ||
| Depression | 3/26 (11.5%) | 0/28 (0%) | ||
| Nervous system disorders | ||||
| Tremor | 3/26 (11.5%) | 5/28 (17.9%) | ||
| Worse Balance | 4/26 (15.4%) | 4/28 (14.3%) | ||
| Increased "off" time | 1/26 (3.8%) | 3/28 (10.7%) | ||
| Psychiatric disorders | ||||
| Visual Hallucinations | 2/26 (7.7%) | 3/28 (10.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 2/26 (7.7%) | 5/28 (17.9%) | ||
| Vascular disorders | ||||
| Increased Blood Pressure | 6/26 (23.1%) | 8/28 (28.6%) | ||
| Decreased Blood Pressure | 3/26 (11.5%) | 4/28 (14.3%) | ||
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 | Daniel Weintraub, MD |
|---|---|
| Organization | University of Pennsylvania |
| Phone | 215-349-8207 |
| Daniel.Weintraub@UPHS.UPENN.EDU |
- 813803