Evaluation of the Efficacy and Safety of Bumetanide in Parkinson's Disease

Study Overview
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Brief Summary
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This is multicentre, proof of concept, randomized, double-blind, parallel-group, placebo-control study in 40 Parkinson's Disease (PD) patients. Patients will be randomized in 2 groups receiving Bumetanide or placebo for 4 months: Group 1 (20 PD patients): bumetanide Group 2 (20 PD patients): placebo intake identically to group 1.

Official Title
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A Randomized Double-blind Placebo-controlled Multicenter Proof-of-concept Trial to Assess the Efficacy and Safety of Bumetanide in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Bumetanide white, oblong, scored tablet
* Drug: Placebo white, oblong, scored tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic Parkinson's disease fulfilling the UK Parkinson's Disease Brain Bank (UKPDSBB) criteria (cf. Appendix VII) 40 < Age < 80 years old Hoehn & Yahr 1.5-4 (OFF stage) Walking and balance or freezing ≥ 1in the MDS-UPDRS II Motor fluctuation defined by a score ≥ 1 on the item time spent in the OFF state of the MDS-UPDRS IV Dose of L-DOPA ≥ 150 mg/d (concomitant treatment) PD medications regimen stable for at least 3 months Patients expected to remain on stable doses of PD medications during all the study Covered by Health Insurance System Able to understand and to sign the informed consent prior to selection Negative pregnancy test at screening Blood Pressure (BP) and Heart Rate (HR) considered Non Clinicaly Significant (NCS) by investigators Electrocardiogram (ECG) recording on a 12-lead ECG considered NCS by investigators Laboratory parameters within the normal range of the laboratory. Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator Exclusion Criteria: Atypical parkinsonism or drug-induced parkinsonism Cognitive impairment (MMSE ≤ 24) Active psychiatric disorder (mood disorders, hallucinations or delirium with strong functional impact and not controlled by medication or which happened during the last 3 months before inclusion) Treatment by Deep Brain Stimulation or continuous infusion of apomorphin/dopa gel Renal or hepatic insufficiency Electrolyte disturbances A corrected QT (QTcF) interval >450ms for male or >470ms for female on the electrocardiogram Any medical condition that might interfere with the protocol except those defined in Section 5.3 Contraindications to bumetanide : persistent anuria, hepatic encephalopathy included coma Women pregnant, nursing or of childbearing age without effective contraception. Patients should not be enrolled if they plan to become pregnant during the time of study participation Patient unable to attend scheduled visits or to comply to the protocol Patient under legal guardianship or judicial protection Patient in the exclusion period of another protocol No possibility of contact in case of emergency Known allergic reactions induced by Burinex (Bumetanide)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Experimental Bumetanide<br>bumetanide with a titration period | Drug: Bumetanide white, oblong, scored tablet<br>* Bumetanide with a titration period<br>|
| Placebo Comparator: Group 2: Placebo comparator<br>placebo intake identically to group 1 | Drug: Placebo white, oblong, scored tablet<br>* placebo intake identically to group 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of this study is the change from baseline (V2) to endpoint (V5) in the MDS-UPDRS III motor score, evaluated 1 hour after the intake of the study treatment (Bumetanide or placebo) in patients in the OFF state. |  | Between Day 1 and Day 120 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from V2 to V5 of the MDS-UPDRS part III and part I measured in a patient in the ON state. | Movement Disorder Society Unified Parkinson's Disease Rating Scale | Between Day 1 and Day 120 | 
| Change of scores of the MDS-UPDRS part II, III and IV during the trial, at D1 (V2), D30 (V3), D60 (V4) and D120 (V5). | Movement Disorder Society Unified Parkinson's Disease Rating Scale | Day 1, Day 30, Day 60, Day 120 | 
| Stand-Walk-Sit test at D1 (V2), D30 (V3), D60 (V4) and D120 (V5). |  | Day 1, Day 30, Day 60, Day 120 | 
| Number of adverse events collected at each visit and phone calls. |  | Throughout the completion of the study, from Day 1 to Day 135 |