Clinical trial NCT03823638: Safety, Tolerability and Effects of Mannitol in Parkinson's Disease
Official title: A Phase II Single Center, Randomized, Double Blind and Placebo Controlled Study Assessing the Safety, Tolerability and Effects of Progressively Increased Dose of Oral Mannitol in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Parkinson Disease
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2019-01-30
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Parkinson's disease is a progressive neurodegenerative disease that causes disabling motor and cognitive impairments. Currently, no disease-modifying therapy exists for this disease. Mannitol, a naturally-occurring substance, which is commonly used as sweetener, was offered as such agent. In this phase II, safety, tolerability-based dose finding, and efficacy study, mannitol or placebo (dextrose) in escalating doses will be given to patients with Parkinson's disease for 36 weeks.


Eligibility criteria: Inclusion Criteria:

1. Ability to understand and signing of informed consent form.
2. Age 40-75 years at the day of visit 1.
3. Diagnosis of Parkinson's disease that is based on the United Kingdom brain bank criteria diagnosed after the age of 40.
4. Stable regime of anti-parkinsonian medication for at least 4 weeks at the day of visit 1.

Exclusion Criteria:

1. Patients with motor deficits that require administration of symptomatic therapy more than 4 times per day at the day of visit 1.
2. Patients on advanced therapy for Parkinson's disease (sub-cutaneous apomorphine, deep brain stimulation or intra-jejunal levodopa infusion).
3. Patients with dementia reflected by a Mini-mental state examination (MoCA) ≥ 24.
4. Patient with legal guardian.
5. History of psychosis or use of dopamine receptor blocking agent on the year proceeding at the visit 1. Quetiapine at dose lower or equal 50 mg per day prescribed for indication other than psychosis is allowed.
6. Suspected Parkinsonian syndrome other than Parkinson's disease.
7. Use of medical marihuana on the month proceeding visit 1.
8. Pregnant or lactating women, or fertile woman who does not use contraceptive. Woman of child-bearing potential must have a negative urine Human chorionic gonadotropin (hCG) and will be monitored by repeated urine tests.
9. Patient with significantly impaired renal functions (urea or creatinine values 20% above the upper norm limit).
10. Diabetes mellitus.
11. Clinical evidence for congestive heart failure.
12. Patient with symptomatic orthostatic hypotension.
13. Based on investigator's opinion, any medical condition that may progress due to consumption of oral mannitol or glucose.

Primary outcomes:
measure: Safety of oral mannitol in Parkinson's disease as assessed by the number of mannitol-related adverse events, clinically significant changes in vital signs and clinically significant abnormalities in laboratory results.
timeFrame: 36 weeks
measure: Tolerability of oral mannitol in Parkinson's disease as assessed by the maximal daily dose (in grams) of mannitol that does not cause discomfort.
timeFrame: 36 weeks
Secondary outcomes:
measure: Time-interval for starting symptomatic therapy (in days) between baseline and week 36, in patients not receiving symptomatic therapy at baseline.
timeFrame: 36 weeks
measure: Change in levodopa-equivalent dose units between baseline and week 36.
timeFrame: 36 weeks
measure: Change of Brief Smell Identification Test (B-SIT) score between baseline and week 36.
timeFrame: 36 weeks
measure: Change in constipation assesment (CAS) score between baseline and week 36.
timeFrame: 36 weeks
measure: Change in Montreal Cognitive Assessment (MoCA) test score between baseline and week 36.
timeFrame: 36 weeks
measure: Change in non-motor symptoms of Parkinson's disease scale (NMSS) between baseline and week 36.
timeFrame: 36 weeks
measure: Change in the ratio of total-to-proteinase K-resistant α-synuclein in red blood cells (RBC) measured by enzyme-linked immunosorbent assay (ELISA)between baseline and week 36.
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
Study officials:
References: