Parkinson Disease Clinical Trial
Official title:
Randomized Cross-Over Study of Fesoterodine on Urgency Episodes in Parkinson's Disease Population
Parkinson's disease (PD) causes several non-motor autonomic symptoms including lower urinary
tract dysfunction. Their symptoms can be managed with antimuscarinics with variable efficacy.
Fesoterodine offers a new therapeutic molecule to target the symptoms of urinary frequency,
urgency and nocturia in this patient population. The purpose of this protocol is to compare
the impact of fesoterodine to placebo on urinary urgency and nocturnal sleep problems in a
heterogeneous population of PD patients in a cross-over fashion.
A representative number of patients with baseline overactive bladder (OAB) symptoms and
Parkinson's disease will be recruited to receive either the active drug or placebo for the
first phase of eight weeks. The groups will then be crossed-over during the second phase of
eight weeks. The main outcomes assessed will be the urgency episodes on a 3-day voiding
diary, as well as the nocturnal sleep problems will be the Parkinson's Disease Sleep Scale
(PDSS).
Study purpose and rationale:
Patients with Parkinson's disease (PD) commonly develop lower urinary tract symptoms as their
disease severity progresses. The most frequent symptoms are nocturia (night time urinary
frequency), urinary frequency and urgency. (1) The effects on voiding function of levodopa
and dopamine agonists for the treatment of motor symptoms in patients with PD are not clearly
understood because studies conclude conflicting results. (2) Their overactive bladder (OAB)
symptoms are primarily managed with antimuscarinics with variable efficacy, and there is
concern for possible heightened central side-effects such as cognitive or motor deterioration
in this patient population. (3, 4) Current standard of care for PD patients with lower
urinary tract symptoms requires a full evaluation with history and physical exam. This is
followed by a microscopic urinalysis, a 3-day bladder diary along with several
questionnaires. According to their symptoms, some patients may require a non-invasive
uroflowmetry and assessment of post void residual, while others will undergo a full
urodynamic studies. Management of their voiding symptoms will require initial conservative
measures and behavioral modifications (reducing caffeinated drinks and smoking cessation,
optimizing fluid intake, weight loss) and bladder training. If this fails to improve their
symptoms, oral pharmacotherapy will be offered with antimuscarinics or beta-3 agonists.
The purpose of this protocol is to compare the impact of fesoterodine to placebo on urinary
urgency and nocturnal sleep problems in a heterogeneous population of PD patients in a
cross-over fashion. Although OAB can be effectively treated, there is compelling and
scientifically sound methodological reasons for its use as participants in the study will not
face additional risks of serious or irreversible harm from exposure to placebo. Placebo
controlled trials are the most rigorous test of treatment efficacy for evaluating a medical
therapy and will require fewer subjects than active control trials. Lastly, anticholinergic
studies have shown to have a very large placebo effect and are only partially effective in
treating voiding symptoms, which justifies the use of a placebo arm.
Sample size:
This is an initial pilot study to identify the effect size of fesoterodine treatment on
urgency episodes in patients with PD.
Subjects will be randomized in both groups by stratifying them according to their age group
(younger or older than 75 years-old) and gender.
Power analysis and sample size calculation are not relevant in this study given its
exploratory nature. The investigators expect to recruit a total of 60 patients to complete
the cross-over study for analysis purposes. This number is based on similar design studies,
particularly one by Wagg et al. looking at the effects of solifenacin and oxybutynin in older
adults with mild cognitive impairment (6). Many other similar studies with groups of subjects
varying between 40 and 77 have demonstrated efficacy differences of anticholinergics in a
cross-over fashion (7-9).
Design and description of methodology:
This randomized, double-blind, placebo-controlled, crossover, parallel-group study will be
carried out in an outpatient clinic. Subjects are assessed and included in the study if they
are willing to participate and fit the criteria at Visit 0. They are then randomized to group
A or B and undergo a baseline evaluation. Both groups undergo a two-week washout period
during which they are given placebo.
Group A subjects will be started on fesoterodine 4 mg once a day in the morning after the
two-week washout period. They will have the option to escalate to 8 mg (2 tablets of 4 mg
each) after 4 weeks on fesoterodine. Patients will have the option to go back to one tablet
(i.e., 4 mg) at any time in the study. At 10 weeks (2 weeks washout and 8 weeks of study
tablets), subjects are assessed in the clinic (Visit 1).
Group B subjects will be started on placebo tablets, similar to fesoterodine 4 mg, and will
have the option to escalate as well.
All subjects then have a 2-week washout period. After the washout period, subjects will be
crossed over to the opposite arm in which the same patterns of outcome assessment and dose
titration were maintained. The study will conclude at 20 weeks. At the end of 20 weeks (Visit
2), the investigators' subjects will be interviewed about any side effects, vital signs will
be examined, adverse reactions or events monitored, and outcome measures will be documented.
Throughout the study, the subjects will be able to drop out anytime with instructions to
inform us of their decision and about any adverse effects. Overall, each subject will have 3
clinical visits after enrollment in the study.
Data analysis plan:
The comparison between the 2 arms of the study, the group that initially received
fesoterodine with the one that received placebo, will be conducted using chi-square analysis.
A 2-sample t test will be used to compare baseline scores between the 2 groups. The Wilcoxon
rank-sum test will be used to calculate whether the mean difference of all the outcome
measures between treatment and placebo periods is significant.
Differences between placebo and treatments will be adjusted by baseline measures (where
available and a 1-sample sign rank tested that the mean difference equated to 0). Any
difference will be analyzed as a change from the baseline.
The primary outcome measure will be the number of urgency episodes, with a P value less than
.05 considered statistically significant. The present statistical analysis of secondary
measures encompasses a number of formal comparisons, and thus a group-wise type I error could
occur.
Recruitment procedures:
Study investigators will send a letter to colleagues asking for referrals of eligible
patients interested in the study. The study investigators may provide the referring
physicians an information sheet about the study to give to the patients. If interested, the
patient will contact the investigator. Or, with documented permission from the patient (e.g.,
note in medical record indicates primary care provider spoke with patient who agreed to be
contacted), the investigaor may be allowed to contact patients about enrollment.
Clinics maintain a separate CHR-approved recruitment protocol that asks patients if they will
agree ahead of time to be contacted for research. Investigators contact patients about the
study in accord with their signed consent. The investigators will consider recruitment when
patients with PD present to their clinic with urination symptoms. They will be presented with
the option and if they agree, they will then be assessed for inclusion. The investigators
will be blinded to the treatment group.
Details on confidentiality:
All data will remain confidential and will be available for access by the investigators only.
All records will be identified with a unique identifier, corresponding to the subjects, to
maintain confidentiality. Records will be kept in one safe and locked location, and
electronic records will be password protected. The study information will be kept for
duration of 25 years.
As this is an investigator-initiated trial, Pfizer Canada's role is restricted to providing
the medications and placebo, as well as the budget required to do the study. They have
approved the current protocol, and will not be involved in further decision-making or data
analysis. There are no other potential conflicts of interest.
Statement on ethical considerations:
The study will be conducted according to ethical principles stated in the Declaration of
Helsinki (2013), ethics approval will be obtained before initiating study-related procedures,
consent forms will take into consideration the well-being, free-will and respect of the
participants, including respect of privacy.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05415774 -
Combined Deep Brain Stimulation in Parkinson's Disease
|
N/A | |
Recruiting |
NCT04691661 -
Safety, Tolerability, Pharmacokinetics and Efficacy Study of Radotinib in Parkinson's Disease
|
Phase 2 | |
Active, not recruiting |
NCT05754086 -
A Multidimensional Study on Articulation Deficits in Parkinsons Disease
|
||
Completed |
NCT04045925 -
Feasibility Study of the Taïso Practice in Parkinson's Disease
|
N/A | |
Recruiting |
NCT04194762 -
PARK-FIT. Treadmill vs Cycling in Parkinson´s Disease. Definition of the Most Effective Model in Gait Reeducation
|
N/A | |
Completed |
NCT02705755 -
TD-9855 Phase 2 in Neurogenic Orthostatic Hypotension (nOH)
|
Phase 2 | |
Terminated |
NCT03052712 -
Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies
|
N/A | |
Recruiting |
NCT05830253 -
Free-living Monitoring of Parkinson's Disease Using Smart Objects
|
||
Recruiting |
NCT03272230 -
Assessment of Apathy in a Real-life Situation, With a Video and Sensors-based System
|
N/A | |
Recruiting |
NCT06139965 -
Validity and Reliability of the Turkish Version of the Comprehensive Coordination Scale in Parkinson's Patients
|
||
Completed |
NCT04580849 -
Telerehabilitation Using a Dance Intervention in People With Parkinson's Disease
|
N/A | |
Completed |
NCT04477161 -
Effect of Ketone Esters in Parkinson's Disease
|
N/A | |
Completed |
NCT03980418 -
Evaluation of a Semiconductor Camera for the DaTSCAN™ Exam
|
N/A | |
Completed |
NCT04942392 -
Digital Dance for People With Parkinson's Disease During the COVID-19 Pandemic
|
N/A | |
Terminated |
NCT03446833 -
LFP Beta aDBS Feasibility Study
|
N/A | |
Completed |
NCT03497884 -
Individualized Precise Localization of rTMS on Primary Motor Area
|
N/A | |
Completed |
NCT05538455 -
Investigating ProCare4Life Impact on Quality of Life of Elderly Subjects With Neurodegenerative Diseases
|
N/A | |
Recruiting |
NCT04997642 -
Parkinson's Disease and Movement Disorders Clinical Database
|
||
Completed |
NCT04117737 -
A Pilot Study of Virtual Reality and Antigravity Treadmill for Gait Improvement in Parkinson
|
N/A | |
Recruiting |
NCT03618901 -
Rock Steady Boxing vs. Sensory Attention Focused Exercise
|
N/A |