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

Parkinson Disease Clinical Trial

— CUREPARK  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03899324
• Other study ID #: CUREPARK/OP105018.BAT
• Status: Recruiting
• Phase: Phase 2
• Start date: April 26, 2019
• Est. completion date: August 2021

Study information

• Verified date: July 2019
• Source: B&A Therapeutics
• Contact: Denis Ravel, PhD
• Phone: 04 38 37 27 40
• Email: denis.ravel[@]initial-rd.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 2021
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Bumetanide white, oblong, scored tablet
Bumetanide with a titration period
• Placebo white, oblong, scored tablet
placebo intake identically to group 1

Locations

Country	Name	City	State
France	Chu Nantes	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
B&A Therapeutics

Country where clinical trial is conducted

France, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Unified dyskinesia rating scale at D1 (V2), D30 (V3), D60 (V4) and D120 (V5).		Day 1, Day 30, Day 60, Day 120
Other	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)
Other	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
Primary	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	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
Secondary	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
Secondary	Stand-Walk-Sit test at D1 (V2), D30 (V3), D60 (V4) and D120 (V5).		Day 1, Day 30, Day 60, Day 120
Secondary	Number of adverse events collected at each visit and phone calls.		Throughout the completion of the study, from Day 1 to Day 135