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

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

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.

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Bumetanide white, oblong, scored tablet; Drug: Placebo white, oblong, scored tablet

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes
    • Contact: LE DILY Séverine; Phone Number: 02 40 16 52 86
    • Principal Investigator: Philippe DAMIER, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Idiopathic Parkinson's disease fulfilling the UK Parkinson's Disease Brain Bank (UKPDSBB) criteria (cf. Appendix VII)
2. 40 < Age < 80 years old
3. Hoehn & Yahr 1.5-4 (OFF stage)
4. Walking and balance or freezing ≥ 1in the MDS-UPDRS II
5. Motor fluctuation defined by a score ≥ 1 on the item "time spent in the OFF state" of the MDS-UPDRS IV
6. Dose of L-DOPA ≥ 150 mg/d (concomitant treatment)
7. PD medications regimen stable for at least 3 months
8. Patients expected to remain on stable doses of PD medications during all the study
9. Covered by Health Insurance System
10. Able to understand and to sign the informed consent prior to selection
11. Negative pregnancy test at screening
12. Blood Pressure (BP) and Heart Rate (HR) considered Non Clinicaly Significant (NCS) by investigators
13. Electrocardiogram (ECG) recording on a 12-lead ECG considered NCS by investigators
14. 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:

1. Atypical parkinsonism or drug-induced parkinsonism
2. Cognitive impairment (MMSE ≤ 24)
3. 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)
4. Treatment by Deep Brain Stimulation or continuous infusion of apomorphin/dopa gel
5. Renal or hepatic insufficiency
6. Electrolyte disturbances
7. A corrected QT (QTcF) interval >450ms for male or >470ms for female on the electrocardiogram
8. Any medical condition that might interfere with the protocol except those defined in Section 5.3
9. Contraindications to bumetanide : persistent anuria, hepatic encephalopathy included coma
10. 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
11. Patient unable to attend scheduled visits or to comply to the protocol
12. Patient under legal guardianship or judicial protection
13. Patient in the exclusion period of another protocol
14. No possibility of contact in case of emergency
15. Known allergic reactions induced by Burinex (Bumetanide)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Unified dyskinesia rating scale at D1 (V2), D30 (V3), D60 (V4) and D120 (V5).	Day 1, Day 30, Day 60, Day 120
Awaken time spent in the OFF state, in the ON state with and without dyskinesia.	Between Day 0 (Screening) and Day 1 (V2), then between Day 60 (V4) and Day 120 (V5)
Patient's Clinical Global Impression (CGI) score at D1 (V2), D30 (V3), D60 (V4) and D120 (V5).	Day 1, Day 30, Day 60, Day 120

Collaborators and Investigators

• Sponsor: B&A Therapeutics

Publications and helpful links

General Publications

• Damier P, Hammond C, Ben-Ari Y. Bumetanide to Treat Parkinson Disease: A Report of 4 Cases. Clin Neuropharmacol. 2016 Jan-Feb;39(1):57-9. doi: 10.1097/WNF.0000000000000114.
• Lozovaya N, Eftekhari S, Cloarec R, Gouty-Colomer LA, Dufour A, Riffault B, Billon-Grand M, Pons-Bennaceur A, Oumar N, Burnashev N, Ben-Ari Y, Hammond C. GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease. Nat Commun. 2018 Apr 12;9(1):1422. doi: 10.1038/s41467-018-03802-y.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2019
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: March 29, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 2, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Bumetanide
• Other Study ID Numbers: CUREPARK/OP105018.BAT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No