Clinical Trial to Evaluate the Safety and Tolerability of Hydrogen in Patients With Parkinson's Disease

This study will investigate the safety and tolerability of molecular hydrogen, a promising antioxidant agent, in patients with early-stage Parkinson's Disease. Subjects will be sequentially randomized in a 1:1 ratio to receive hydrogen-enriched water or the corresponding placebo twice a day, in addition to all standard-of-care treatments. Enrollment goal is 70 subjects. Duration of therapy is 52 weeks.

The primary outcome measures are safety and tolerability of hydrogen-enriched water. Secondary outcome measures include: progression of motor symptoms, health-related quality of life, progression of cognitive decline, and progression of symptom burden.

• Hydrogen (Drug): each hydrogen tablet contains 80mg magnesium
• Placebo oral tablet (Drug): matching placebo tablet

Primary outcomes

• Number of Treatment-emergent Adverse Events [56 weeks]: Number of treatment-emergent adverse events \[safety and tolerability\] of H2-enriched water in patients with Parkinson's disease (PD).

Secondary outcomes

• Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [56 weeks]: Change from baseline to week 56 in motor examination, as assessed by score on Part III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part III of the MDS-UPDRS assesses the motor signs of Parkinson's Disease. Scores range from 0-33 with a lower score indicating less severe impairment.
• Score on the Parkinson's Disease Quality of Life Questionnaire (PDQ-39) [56 weeks]: Change from baseline to week 56 in Parkinson's Disease-related quality of life as assessed by the Parkinson's Disease Quality of Life Questionnaire (PDQ-39). The PDQ-39 assesses how often patients experience difficulties across 8 quality of life domains (mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication, and bodily discomfort). Scores for each domain range from 0 to 100 with lower scores indicating more impaired quality of life. The overall score is an average of the scores for the 8 dimensions.
• Score on the Montreal Cognitive Assessment (MoCA) [56 weeks]: Change from baseline to week 56 in overall cognitive function as assessed by the Montreal Cognitive Assessment (MoCA) score. Scores on the MoCA range from 0-30 with lower scores indicating more cognitive impairment.
• Score on the Combined Part I, Part II, Part III, and Part IV Subscales of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [56 weeks]: Change from baseline to week 56 on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UPDRS consists of four sub-scales. For each sub-scale, lower scores indicate less severe impairment. The scales are: Part I, non-motor experiences of daily living (scores range from 0-52); Part II, motor experiences of daily living (scores range from 0-52); Part III, motor examination (scores range from 0-132) and part IV, motor complications (scores range from 0-24). Score for the total assessment ranges from 0 to 260 with lower scores indicating less severe impairment.

Sex: All, ages: 40 Years to 80 Years

Inclusion Criteria:

* Diagnosis of Parkinson's Disease
* Modified Hoehn \& Yahr Stage < III
* Diagnosis of Parkinson's Disease made within past 3 years•
* Ability to complete questionnaires
* Willingness to go off parkinsonian medication for 12 hours prior to baseline and 56-week assessments

Exclusion Criteria:

* Other major diseases of the central nervous system
* History of stroke
* Use of antipsychotic neuroleptic medication within the last 6 months
* Symptomatic (secondary) parkinsonism
* Atypical parkinsonian variants
* Unstable medical or psychiatric illness
* Known kidney disease
* History of stereotactic brain surgery
* Significant cognitive impairment
* Inability to safely tolerate 8 ounces of water twice daily associated with the study medication
* Unable to avoid regular use of medications containing magnesium
* Treatment with another investigational drug within the last 30 days that may interfere with the study medication
* Pregnancy or nursing

Participant flow

Outcome results

• Number of Treatment-emergent Adverse Events (Primary), Number, Adverse Events: Hydrogen Tablets 0; Placebo Tablets 0
• Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Secondary)
• Score on the Parkinson's Disease Quality of Life Questionnaire (PDQ-39) (Secondary)
• Score on the Montreal Cognitive Assessment (MoCA) (Secondary)
• Score on the Combined Part I, Part II, Part III, and Part IV Subscales of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Secondary)

Adverse events

Time frame: 56 Weeks

Limitations and caveats: Due to low enrollment in this study, we are not able to report on study outcome measures for participants and are unable to draw conclusions.

• Study Protocol and Statistical Analysis Plan (PDF, 2020-04-21)

• Carine Maurer, MD,PhD, Principal investigator, Stony Brook University