Parkinson Disease
Conditions
Brief 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.
Interventions
DRUGBumetanide white, oblong, scored tablet
Bumetanide with a titration period
DRUGPlacebo white, oblong, scored tablet
placebo intake identically to group 1
Sponsors
B&A Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). | Day 1, Day 30, Day 60, Day 120 | Movement Disorder Society Unified Parkinson's Disease Rating Scale |
| Change from V2 to V5 of the MDS-UPDRS part III and part I measured in a patient in the ON state. | Between Day 1 and Day 120 | Movement Disorder Society Unified Parkinson's Disease Rating Scale |
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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) |
| Unified dyskinesia rating scale at D1 (V2), D30 (V3), D60 (V4) and D120 (V5). | Day 1, Day 30, Day 60, Day 120 |
Countries
France
Contacts
Primary ContactDenis Ravel, PhD
Backup ContactFanny Kayser
Outcome results
None listed