Safety, Tolerability and Effects of Mannitol in Parkinson's Disease (PD-mannitol)

January 29, 2019 updated by: ARKADIR DAVID, Hadassah Medical Organization

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

36 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: D-Mannitol
Oral Supplement of the investigated substance: D-Mannitol powder (manufacturer Roquette)
Dietary supplement: Oral D-Mannitol of Placebo
Gradually increased doses of oral D-Mannitol of Placebo (Dextrose monohydrate)
Placebo Comparator: Placebo
Oral Supplement of the placebo: Dextrose monohydrate powder (manufacturer Roquette)
Dietary supplement: Oral D-Mannitol of Placebo
Gradually increased doses of oral D-Mannitol of Placebo (Dextrose monohydrate)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 36 weeks
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.
Time Frame: 36 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time-interval for starting symptomatic therapy (in days) between baseline and week 36, in patients not receiving symptomatic therapy at baseline.
Time Frame: 36 weeks
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.
36 weeks
Change in levodopa-equivalent dose units between baseline and week 36.
Time Frame: 36 weeks
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.
36 weeks
Change of Brief Smell Identification Test (B-SIT) score between baseline and week 36.
Time Frame: 36 weeks
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.
36 weeks
Change in constipation assesment (CAS) score between baseline and week 36.
Time Frame: 36 weeks
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.
36 weeks
Change in Montreal Cognitive Assessment (MoCA) test score between baseline and week 36.
Time Frame: 36 weeks
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.
36 weeks
Change in non-motor symptoms of Parkinson's disease scale (NMSS) between baseline and week 36.
Time Frame: 36 weeks
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.
36 weeks
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.
Time Frame: 36 weeks
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.
36 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hadassah Medical Organization

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 20, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 30, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 30, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0346-17-HMO-CTIL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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