Safety, Tolerability and Effects of Mannitol in Parkinson's Disease

NCT03823638 | Unknown Phase 2

• 1 other identifier: 0346-17-HMO-CTIL
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  Safety will be assessed by the number of treatment-related adverse events, number of patients with clinically significant change of vital signs (supine and standing blood pressure and pulse) and number of patients with clinically significant change in laboratory results (electrolytes, renal and liver functions, blood count).

  36 weeks

• Tolerability of oral mannitol in Parkinson's disease as assessed by the maximal daily dose (in grams) of mannitol that does not cause discomfort.

  Tolerability of oral mannitol in Parkinson's disease as assessed by the maximal daily dose (in grams, up to 18 grams per day) of mannitol that does not cause discomfort based on the subjective report by the patient.

  36 weeks

Secondary Outcomes (7)

• Time-interval for starting symptomatic therapy (in days) between baseline and week 36, in patients not receiving symptomatic therapy at baseline.

  36 weeks

• Change in levodopa-equivalent dose units between baseline and week 36.

  36 weeks

• Change of Brief Smell Identification Test (B-SIT) score between baseline and week 36.

  36 weeks

• Change in constipation assesment (CAS) score between baseline and week 36.

  36 weeks

• Change in Montreal Cognitive Assessment (MoCA) test score between baseline and week 36.

  36 weeks

Study Arms (2)

D-Mannitol

EXPERIMENTAL

Oral Supplement of the investigated substance: D-Mannitol powder (manufacturer Roquette)

Dietary Supplement: Oral D-Mannitol of Placebo

Placebo

PLACEBO COMPARATOR

Oral Supplement of the placebo: Dextrose monohydrate powder (manufacturer Roquette)

Dietary Supplement: Oral D-Mannitol of Placebo

Interventions

Oral D-Mannitol of Placebo DIETARY_SUPPLEMENT

Gradually increased doses of oral D-Mannitol of Placebo (Dextrose monohydrate)

D-Mannitol; Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients with motor deficits that require administration of symptomatic therapy more than 4 times per day at the day of visit 1.
• Patients on advanced therapy for Parkinson's disease (sub-cutaneous apomorphine, deep brain stimulation or intra-jejunal levodopa infusion).
• Patients with dementia reflected by a Mini-mental state examination (MoCA) ≥ 24.
• Patient with legal guardian.
• 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.
• Suspected Parkinsonian syndrome other than Parkinson's disease.
• Use of medical marihuana on the month proceeding visit 1.
• 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.
• Patient with significantly impaired renal functions (urea or creatinine values 20% above the upper norm limit).
• Diabetes mellitus.
• Clinical evidence for congestive heart failure.
• Patient with symptomatic orthostatic hypotension.
• Based on investigator's opinion, any medical condition that may progress due to consumption of oral mannitol or glucose.

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Center

Jerusalem, 91120, Israel

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

David Arkadir, MD PhD

CONTACT

02-6777716; arkadir@hadassah.org.il

Anna Linetsky

CONTACT

02-6777716; annalin@hadassah.org.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: January 30, 2019
• Study Start: November 20, 2018
• Primary Completion: July 1, 2020
• Study Completion: December 31, 2020
• Last Updated: January 30, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)