Parkinson DiseasePhase 2PD-mannitolNCT03823638
Safety, Tolerability and Effects of Mannitol in Parkinson's Disease
A Phase 2 study of Parkinson Disease, run by Hadassah Medical Organization at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Parkinson Disease
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- 20 Nov 2018to 31 Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Hadassah Medical Center
Jerusalem, 91120
David Arkadir, MD PhD, 02-6777716, arkadir@hadassah.org.il
Anna Linetsky, 02-6777716, annalin@hadassah.org.il
About this study
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
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
- Being tested
- Oral D-Mannitol of Placebo
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral D-Mannitol of PlaceboDietary supplement
Gradually increased doses of oral D-Mannitol of Placebo (Dextrose monohydrate)
| Study group | Role | What they receive |
|---|---|---|
| D-Mannitol | Experimental | Oral Supplement of the investigated substance: D-Mannitol powder (manufacturer Roquette) Receives: Dietary Supplement: Oral D-Mannitol of Placebo |
| Placebo | Placebo comparator | Oral Supplement of the placebo: Dextrose monohydrate powder (manufacturer Roquette) Receives: Dietary Supplement: Oral D-Mannitol of Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
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.
Measured: 36 weeks
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.
Measured: 36 weeks
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.
Measured: 36 weeks
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.
Measured: 36 weeks
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.
Measured: 36 weeks
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.
Measured: 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.
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.
Measured: 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2019
- Study start20 Nov 2018
- Primary completion1 Jul 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ARKADIR DAVID, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03823638
- Sponsor's protocol ID
- 0346-17-HMO-CTIL
- Acronym
- PD-mannitol
- Status last verified
- Jan 2019
- First submitted
- 20 Nov 2018
- Last updated
- 30 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03823638
- Acronym / sponsor ID
- PD-mannitol / 0346-17-HMO-CTIL
- Conditions
- Parkinson Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- 20 Nov 2018 (actual)
- Primary completion
- 1 Jul 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 30 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-Mannitol | Experimental | Dietary Supplement: Oral D-Mannitol of PlaceboOral Supplement of the investigated substance: D-Mannitol powder (manufacturer Roquette) |
| Placebo | Placebo comparator | Dietary Supplement: Oral D-Mannitol of PlaceboOral Supplement of the placebo: Dextrose monohydrate powder (manufacturer Roquette) |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral D-Mannitol of PlaceboGradually increased doses of oral D-Mannitol of Placebo (Dextrose monohydrate) | Dietary supplement | D-Mannitol, Placebo |
Primary outcome
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).
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.
7 secondary outcomes
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
Change in levodopa-equivalent dose units between baseline and week 36.
Time frame: 36 weeks
Change of Brief Smell Identification Test (B-SIT) score between baseline and week 36.
Time frame: 36 weeks
Change in constipation assesment (CAS) score between baseline and week 36.
Time frame: 36 weeks
Change in Montreal Cognitive Assessment (MoCA) test score between baseline and week 36.
Time frame: 36 weeks
Change in non-motor symptoms of Parkinson's disease scale (NMSS) between baseline and week 36.
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Parkinson Disease, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact David Arkadir, MD PhD (02-6777716, arkadir@hadassah.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 36 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2019.