Clinical trial NCT02536976: Mirabegron in Parkinson Disease and Impaired Cognition
Official title: A Clinical Trial of Mirabegron for Overactive Bladder Symptoms in Patients With Parkinson Disease and Impaired Cognition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Overactive Bladder
Impaired Cognition
Keywords: mirabegron
Lead sponsor: HealthPartners Institute
Sponsor class: OTHER
First posted: 2015-09-01
Enrollment: 7
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is a high prevalence of OAB symptoms among patients with Parkinson's disease and a lack of pharmacotherapies with an acceptable side effect profile. Specifically, available anticholinergic medications have a high risk of cognitive side-effects, which preclude their use in PD patients with CI. PD can also cause a number of non-motor symptoms that are likely to be adversely affected by the currently available anticholinergic agents. Mirabegron is the first pharmacologic treatment which may not exacerbate CI, constipation, orthostatic hypotension (OH), somnolence, and dry mouth in PD.


Eligibility criteria: INCLUSION CRITERIA:

1. Aged 25-80 at screening. Subjects older than 80 will be allowed at the discretion of the PI.
2. Ambulatory (defined as able to ambulate at least 10 meters, with or without assistance).
3. Clinical Diagnosis of PD based on the United Kingdom Brain Bank diagnostic criteria for PD.
4. At baseline visit (Visit 2) patients must have:

   * At least 8 micturitions per 24 hours and
   * At least 3 urgency episodes per 3-day diary.
5. A MoCA score between 19 and 28 (inclusive) at screening. For those on cognitive enhancers (donepezil, rivastigmine, memantine, galantamine) a MoCA score between 19 and 29 (inclusive) at screening.
6. Provide informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.
7. Be cognitively capable, in the opinion of investigator, to understand and provide such informed consent.
8. Be cognitively capable to complete the required questionnaires and assessments, OR have a care partner who is willing and capable to assist them in the completion of these tasks.
9. Be on a stable regimen of antiparkinson's medications at least 30 days prior to screening, and be expected to remain on a stable dose for the duration of the study.
10. If taking cognitive enhancers (donepezil, rivastigmine, memantine, galantamine), must be on stable dose at least 30 days prior to screening, and be expected to remain on a stable dose for the duration of the study.

EXCLUSION CRITERIA:

1. Known or suspected alcohol or substance abuse in the preceding 12 months.
2. Women who are pregnant or breastfeeding.
3. Women of childbearing potential (WOCP) who are not using at least one method of contraception.
4. Patients with severe renal impairment (CLcr ≤ 29 mL/min, or eGFR ≤ 29 mL/min/1.73 m2), or moderate or severe hepatic impairment (Child-Pugh classes B or C).
5. Patients with bladder outlet obstruction (BOO) that, in the opinion of the study urologist, would expose them to risk of urinary retention during treatment with mirabegron.
6. Patients treated with drugs metabolized by the CYP2D6 pathway.
7. Patients with supine systolic blood pressure (SBP) ≥ 180 mm Hg, or diastolic blood pressure (DBP) ≥ 110 mm Hg.
8. Clinically significant, uncontrolled cardiac arrhythmia, unstable angina, congestive heart failure (NYHA Class 3 or 4), or history of myocardial infarction in the preceding 2 years.
9. History of cancer in the preceding 2 years other than successfully treated, non-metastatic, squamous cell or basal cell carcinoma, or cervical cancer in situ.
10. Any major urological procedure in the preceding 90 days.
11. Any major surgical procedure in the preceding 30 days.
12. Previously treated with mirabegron within 60 days prior to the baseline visit (Visit 2), or previously having failed treatment with mirabegron regardless of duration and timing of treatment.
13. Current or previous, within the 60 days preceding the baseline visit (Visit 2), treatment with antimuscarinic agents for OAB symptoms; and, willingness to not use antimuscarinic agents for the duration of the study.
14. Currently receiving any other investigational drug or having received an investigational drug within the 60 days preceding the baseline visit (Visit 2).
15. Any condition or laboratory test result, which, in the opinion of the Investigator or the Study Urologist, might result in an increased risk to the patient, or would affect their participation in the study.
16. Any patient who, in the opinion of the Investigator, is not a good candidate for the study or will not be able to follow study procedures.

Primary outcomes:
measure: Change in Montreal Cognitive Assessment Total Score
timeFrame: From Week 2 to Week 14
Secondary outcomes:
measure: Change in Overactive Bladder Questionnaire Subscale Scores
timeFrame: From Week 2 to Week 14
measure: Change in Unified Parkinson's Disease Rating Scale
timeFrame: From Week 2 to Week 14
Other outcomes:
Locations:
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center
state: Minnesota
Study officials:
affiliation: Struthers Parkinson's Center
name: Sotirios A Parashos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: