Back to resultsSafety, Tolerability and Effects of Mannitol in Parkinson's Disease (PD-mannitol)
Primary Purpose
Parkinson Disease
Status
Unknown status
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Oral D-Mannitol of Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Hadassah Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
D-Mannitol
Placebo
Arm Description
Oral Supplement of the investigated substance: D-Mannitol powder (manufacturer Roquette)
Oral Supplement of the placebo: Dextrose monohydrate powder (manufacturer Roquette)
Outcomes
Primary Outcome Measures
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).
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.
Secondary Outcome Measures
Time-interval for starting symptomatic therapy (in days) between baseline and week 36, in patients not receiving symptomatic therapy at baseline.
Median time interval will be reported. P-Values as assessed by Mann-Whitney test will be reported. Longer time interval will be considered as a better outcome.
Change in levodopa-equivalent dose units between baseline and week 36.
Total levodopa-equivalent dose (LED units) will be calculated based on Tomlinson, Mov Disord 2010. P-Values as assessed by Mann-Whitney test will be reported. Smaller change will be considered as a better outcome.
Change of Brief Smell Identification Test (B-SIT) score between baseline and week 36.
Median and range of change will be reported. P-Values as assessed by Mann-Whitney test will be reported. Higher absolute positive value (reflecting improved smell) or lower absolute negative value (slower deterioration) will be considered as better outcomes.
Change in constipation assesment (CAS) score between baseline and week 36.
Median and range of change will be reported. Change in score will be reported. P-Values as assessed by Mann-Whitney test will be reported. Lower absolute positive value or higher absolute negative value will be considered as better outcomes.
Change in Montreal Cognitive Assessment (MoCA) test score between baseline and week 36.
P-Values as assessed by Mann-Whitney test will be reported. Higher absolute positive value or lower absolute negative value will be considered as better outcomes.
Change in non-motor symptoms of Parkinson's disease scale (NMSS) between baseline and week 36.
Median and range of change will be reported. P-Values as assessed by Mann-Whitney test will be reported. Lower absolute positive value or higher absolute negative value will be considered as better outcomes.
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.
Median and range of change will be reported. P-Values as assessed by Mann-Whitney test will be reported. Higher absolute positive value or lower absolute negative value will be considered as better outcomes.
Full Information
NCT ID
NCT03823638
First Posted
November 20, 2018
Last Updated
January 29, 2019
Sponsor
Hadassah Medical Organization
1. Study Identification
Unique Protocol Identification Number
NCT03823638
Brief Title
Safety, Tolerability and Effects of Mannitol in Parkinson's Disease
Acronym
PD-mannitol
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
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 20, 2018 (Actual)
Primary Completion Date
July 1, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hadassah Medical Organization
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
D-Mannitol
Arm Type
Experimental
Arm Description
Oral Supplement of the investigated substance: D-Mannitol powder (manufacturer Roquette)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral Supplement of the placebo: Dextrose monohydrate powder (manufacturer Roquette)
Intervention Type
Dietary Supplement
Intervention Name(s)
Oral D-Mannitol of Placebo
Intervention Description
Gradually increased doses of oral D-Mannitol of Placebo (Dextrose monohydrate)
Primary Outcome Measure Information:
Title
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.
Description
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).
Time Frame
36 weeks
Title
Tolerability of oral mannitol in Parkinson's disease as assessed by the maximal daily dose (in grams) of mannitol that does not cause discomfort.
Description
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.
Time Frame
36 weeks
Secondary Outcome Measure Information:
Title
Time-interval for starting symptomatic therapy (in days) between baseline and week 36, in patients not receiving symptomatic therapy at baseline.
Description
Median time interval will be reported. P-Values as assessed by Mann-Whitney test will be reported. Longer time interval will be considered as a better outcome.
Time Frame
36 weeks
Title
Change in levodopa-equivalent dose units between baseline and week 36.
Description
Total levodopa-equivalent dose (LED units) will be calculated based on Tomlinson, Mov Disord 2010. P-Values as assessed by Mann-Whitney test will be reported. Smaller change will be considered as a better outcome.
Time Frame
36 weeks
Title
Change of Brief Smell Identification Test (B-SIT) score between baseline and week 36.
Description
Median and range of change will be reported. P-Values as assessed by Mann-Whitney test will be reported. Higher absolute positive value (reflecting improved smell) or lower absolute negative value (slower deterioration) will be considered as better outcomes.
Time Frame
36 weeks
Title
Change in constipation assesment (CAS) score between baseline and week 36.
Description
Median and range of change will be reported. Change in score will be reported. P-Values as assessed by Mann-Whitney test will be reported. Lower absolute positive value or higher absolute negative value will be considered as better outcomes.
Time Frame
36 weeks
Title
Change in Montreal Cognitive Assessment (MoCA) test score between baseline and week 36.
Description
P-Values as assessed by Mann-Whitney test will be reported. Higher absolute positive value or lower absolute negative value will be considered as better outcomes.
Time Frame
36 weeks
Title
Change in non-motor symptoms of Parkinson's disease scale (NMSS) between baseline and week 36.
Description
Median and range of change will be reported. P-Values as assessed by Mann-Whitney test will be reported. Lower absolute positive value or higher absolute negative value will be considered as better outcomes.
Time Frame
36 weeks
Title
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.
Description
Median and range of change will be reported. P-Values as assessed by Mann-Whitney test will be reported. Higher absolute positive value or lower absolute negative value will be considered as better outcomes.
Time Frame
36 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Arkadir, MD PhD
Phone
02-6777716
Email
arkadir@hadassah.org.il
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Linetsky
Phone
02-6777716
Email
annalin@hadassah.org.il
Facility Information:
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Arkadir, MD PhD
Phone
02-6777716
Email
arkadir@hadassah.org.il
First Name & Middle Initial & Last Name & Degree
Anna Linetsky
Phone
02-6777716
Email
annalin@hadassah.org.il
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety, Tolerability and Effects of Mannitol in Parkinson's Disease
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