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The Effects of the Rivastigmine Patch on Parkinson's Disease With Memory and/or Thinking Problems

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Bruce Miller, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00988117
First received: September 29, 2009
Last updated: January 24, 2014
Last verified: January 2014

September 29, 2009
January 24, 2014
April 2010
April 2011   (final data collection date for primary outcome measure)
  • Resting State Functional Activity Change From Baseline to 12 Weeks [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Fractional amplitude of low frequency fluctuations (fALFF) was used to measure brain activity. This metric is derived from task-free functional magnetic resonance imaging (fMRI) and represents the power of regional spontaneous and intrinsic brain activity at the local, voxel-wise level while the subject is at rest. More specifically, the amplitude of low-frequency fluctuations (ALFF) is the total power in the low-frequency range, and fALFF is calculated by dividing ALFF by the total power across all measurable frequencies. Whereas ALFF values increase near blood vessels and cerebrospinal fluid (CSF), likely due to pulsations in those areas, fALFF is less susceptible to artifactual signals. We measured change in these ratio scores post-treatment minus baseline and present in z-score units.
  • Pre-post Change in Continuous Performance Test of Attention (Median Reaction Time) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    On the Continuous Performance Test (CPT), subjects press the spacebar quickly when they see a target image (a white star; 150 trials), and withhold response when they see a non-target image (5 randomly sampled white shapes; 150 trials). The inter-stimulus interval is randomly sampled from 1.5s, 2.5s, or 4s. Performance is measured by the median reaction time (milliseconds) on accurate target trials.
  • The Attention Network Test (overall reaction time) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Resting state functional network activity (degree of fit in the dorsolateral frontal-parietal network) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Fluctuations in attention (One Day Fluctuation Assessment Scale) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Neuropsychiatric symptoms (Neuropsychiatric Inventory total score) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00988117 on ClinicalTrials.gov Archive Site
Pre-post Change in Montreal Cognitive Assessment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
The Montreal Cognitive Assessment (MoCA) was used as measure of global cognitive function. Total scores range from 0 (worst) to 30 (best).
  • Changes in everyday functions (Functional Assessment Questionnaire) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Caregiver assessment of cognitive and functional changes (Clinical Dementia Rating) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Assessment of depression (Geriatric Depression Scale) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Assessment of anxiety levels (Beck Anxiety Inventory) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Assessment of global decline (Clinical Global Impression of Change) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
The Effects of the Rivastigmine Patch on Parkinson's Disease With Memory and/or Thinking Problems
The Effects of the Rivastigmine Patch on Attention and Behavior in Parkinson's Disease With Dementia (PDD)

This is an open-label study to investigate the effects of the rivastigmine patch on attention and behavior in Parkinson's disease when associated with memory and/or thinking problems. Rivastigmine (also sold under the name Exelon) is an FDA approved medication used for the treatment of mild to moderate Alzheimer's Disease (AD) and memory or thinking problems due to Parkinson's disease. Recently a rivastigmine patch was developed, which has shown similar effectiveness with fewer side effects and increased caregiver preference when compared to capsules. This is an open-label 12 week study where 15 subjects diagnosed with Parkinson's Disease who have mild to moderate memory and/or thinking complaints will be treated with the rivastigmine patch at UCSF. This study also analyzes the mechanism by which the rivastigmine patch works in people with Parkinson's disease and memory and/or thinking problems.

Participation in this study requires four visits: a screening visit to ensure eligibility, an initial/baseline visit where the medication is distributed at a dosage lower than the optimal recommended dosage, a four week follow-up visit where the dosage of the medication is increased to the optimal amount, and a final twelve week follow up visit.

  • In the screening visit the patient will undergo a neurological exam (including a review of their medical history and short physical exam), electrocardiogram ( a painless procedure that measures electrical activity of your heart), cognitive testing (such as memory and thinking tests), and a blood draw.
  • At the Baseline/Initial visit the patient will receive a brief physical exam, additional cognitive testing, and an MRI scan. Afterwards, the study drug will be distributed.
  • At the four week follow up visit the patient will be asked to do some abbreviated cognitive and neurological testing and the study drug will be re-distributed at the target dosage.
  • At the final twelve week visit the patient will receive additional cognitive and neurological testing, and an MRI scan.
  • Study compliance and adverse events will be reviewed every two weeks throughout the study, whether in person or over the phone.
Interventional
Phase 4
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Parkinsons Disease With Dementia
  • Parkinsons Disease With Mild to Moderate Memory and/or Thinking Problems
Drug: Rivastigmine Patch 9.5 cm2
Subjects will be started on a 5cm2/24hr rivastigmine patch. After 4 weeks, the dose will be increased to a recommended target dose of 9.5cm2/24hr patch for 8 additional weeks.
Experimental: Rivastigmine Patch 9.5 cm2
Intervention: Drug: Rivastigmine Patch 9.5 cm2
Possin KL, Kang GA, Guo C, Fine EM, Trujillo AJ, Racine CA, Wilheim R, Johnson ET, Witt JL, Seeley WW, Miller BL, Kramer JH. Rivastigmine is associated with restoration of left frontal brain activity in Parkinson's disease. Mov Disord. 2013 Sep;28(10):1384-90. doi: 10.1002/mds.25575. Epub 2013 Jul 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
April 2011
April 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Must meet research criteria for Parkinson's Disease with Dementia (PDD)
  • Males and females, ages between 55 and 100
  • Able to undergo psychometric testing
  • Mini-Mental State Examination ≥ 21 and Clinical Dementia Rating < 2
  • Reliable informant with frequent contact with patient

Exclusion Criteria:

  • Non-English speaking, as cognitive tests will be in English
  • Evidence of other neurological or psychiatric disorders which preclude diagnosis of PDD (including, but not limited to, stroke, any psychotic disorder, severe bipolar or unipolar depression, seizure disorder, or head injury with loss of consciousness) within the past year
  • Concurrent treatment with any acetylcholinesterase inhibitors (including rivastigmine in pill or patch form), antipsychotic agents (excluding quetiapine in dosages of 150 mg and lower, abilify and geodon as these medications are commonly used in treatment of Parkinson's Disease (PD) psychosis and should not affect results of study), mood stabilizers (valproate or lithium) or benzodiazepines (other than temazepam or zolpidem)
  • Positive urine drug screen or suspected alcohol or substance abuse within last 1 year
  • Current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease. If the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included
  • Systolic blood pressure over 180 or less than 90 mm Hg. Diastolic blood pressure not greater than 105 or less than 50 mm Hg
  • ECG is abnormal and judged to be clinically significant by the investigator
  • Use of investigational drugs or participation in investigational drug studies within 30 days of screening
  • Geriatric Depression Score score > 15/30
  • Hachinski score > 4
Both
55 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00988117
CENA7 13D US45T
Yes
Bruce Miller, University of California, San Francisco
University of California, San Francisco
Novartis
Principal Investigator: Bruce Miller, M.D. UCalifornia SF
Study Director: Joel Kramer, PsyD UCalifornia SF
University of California, San Francisco
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP