- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03403309
Inosine 5'-Monophosphate to Raise of Serum Uric Acid Level in Patients With Multiple System Atrophy: a Multi-center, Randomized Controlled, Double Blind, Parallel Assigned Clinical Trial
Inosine 5'-Monophosphate to Raise of Serum Uric Acid Level in Patients With Multiple System Atrophy: a Multi-center, Randomized Controlled, Double Blind, Parallel Assigned Clinical Trial (IMPROVE MSA Study)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background and objective:
Uric acid (UA) is the end product of purine metabolism in human body, which is converted from the precursor metabolite inosine and finally excreted via route of urine and gastrointestinal tract. A high level of UA, usually ≥ 7.0 mg/dL, may lead to development of gout, nephrolithiasis, or to give detrimental effect to a variety of medical diseases, such as chronic kidney disease, cardiovascular disorders, and diabetes. Meanwhile, UA is the very well-known antioxidant, in which the biological antioxidant act as scavenging free radicals (e.g. peroxynitrite), chelating iron, and preventing peroxidation of lipid. Although there have been two faced aspects on UA, antioxidant versus pro-inflammatory potentials, toward neurodegenerative disorders, converging evidences have been highlighting the effects of potential disease modification so far. Given the certain contribution of oxidative stress to the pathogenesis of various neurodegenerative disorders, a therapeutic attempts to anti-oxidation may be promising and feasible. In observational study, ample evidence has been suggested to be beneficial associations between higher uric acid level and lower the risk of disease, clinical severity and progression in Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, and even up to myasthenia gravis across clinical, epidemiological, and radiological studies. In addition, on aspect of interventional study, there have been 4 randomized clinical trials of increasing serum uric acid via administration of inosine so far in multiple sclerosis, stroke, amyotrophic lateral sclerosis, and Parkinson's disease. All of the studies have demonstrated reliable capability of increasing serum uric acid level, and favorable safety and tolerability profile. Currently, a phase II trial in Parkinson's disease demonstrated hopeful view in disease modifying strategy by modulating disease progression rate on the inosine administered group with a dose dependent manner.
In case of multiple system atrophy (MSA), there have been a couple of previous reports including increased serum level of UA in MSA compared to healthy control, and strong correlation in serum uric acid level with either motor or cognitive functions. However, no interventional studies have been undertaken to date at all regarding UA. We aimed to investigate the UA elevating capability, safety, and tolerability of inosine 5'-monophosphate, a precursor of uric acid, in MSA patients with randomized, placebo controlled, and parallel assigned design.
Methods:
All participants are randomized to study drugs, either tablet of placebo or inosine 5'-monophosphate, in 1 to 1 ratio and then undergo scheduled titration. Study drugs are initiated with 1 tablet 2 times per day, and then titrate up by 1 tablet per every visit up to visit 2. That is, 1 tablet two times per day for initial 2 weeks, 1 tablet three times per day from next week 3 to 4, and 2 tablets two times per day from next week 4 to 6, and then maintain throughout to week 24. Laboratory tests including serum uric acid level, urine analysis, and stone analysis are scheduled to be checked at time of week 2, 4, 6, 12, 18, and 24, respectively. A maximum limit of elevated serum uric acid level is 9 mg/dL, and thus reducing dose of administration may be considered in case of exceeding the limited level. Comparison of the extent of altered serum uric acid level, safety, and tolerability from baseline to week 24 will be analyzed after study termination.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
Seou
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Seoul, Seou, Korea, Republic of, 120-752
- Department of Neurology, Yonsei University College of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects who met the clinical criteria of either probable or possible multiple system atrophy, age ranged from 19 to 75 at their onset of symptom.
- Subjects who underwent brain magnetic resonance imaging or 18F-fluorodeoxyglucose positron emission tomography at the time of their diagnosis in which showed any findings compatible to multiple system atrophy, such as cerebellar or putaminal atrophy, putaminal hyperintense rim or iron accumulation, hot cross bun sign or T2 high signal intensities on middle cerebellar peduncle, and decreased glucose metabolism on putamen or cerebellum.
- Total score of unified multiple system atrophy rating scale 30 or more at baseline screening.
- Serum uric acid level ≤ 6.0 mg/dL at baseline screening.
Exclusion Criteria:
- Prior history of gout, nephrolithiasis, stroke, or chronic kidney disease.
- Presentation of urine pH ≤ 5.0 or uric acid crystalluria on urine analysis at baseline screening.
- Subject who showed febrile condition or have any sort of unstable and hopeless disorders.
- Subjects on following medications undergo 4 weeks of wash-out period, and then not co-administered at all over study duration: co-enzyme Q, creatine, daily vitamin E 50 IU or more, and daily vitamin C 300 mg or more.
- Presence of psychiatric or cognitive impairment by which interrupt to carry out the whole process of the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Inosine 5'-monophosphate arm
Subjects are treated with inosine 5'-monophosphate to increase serum uric acid level.
|
1) Subjects are initiated with 1 tablet (500mg of inosine 5'-monophosphate per one tablet) two times per day, and then titrated up by 1 tablet per every visit up to visit 2, i.e. increased up to 2 tablets two times a day by week 6.
A maximum limit of elevated serum uric acid level is 9 mg/dL, so that reducing dose of administration may be considered in case of being way over the top of limited level.
|
Placebo Comparator: Placebo arm
Subjects are treated with placebo not to increase serum uric acid level.
|
2) Subjects are initiated with 1 tablet (500mg of placebo tablet with inactive therapeutic effect) two times a day, and then titrated up by 1 tablet per every visit up to visit 2, i.e. increased up to 2 tablets two times a day by week 6.
A maximum limit of elevated serum uric acid level is 9 mg/dL.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum uric acid elevation
Time Frame: Baseline to Week 24
|
Serum uric acid elevation is defined as an altered level of serum uric acid from baseline to week 24.
A laboratory test is scheduled to be checked at time of week 2, 4, 6, 12, 18, and 24, respectively.
|
Baseline to Week 24
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Safety
Time Frame: Baseline to Week 24
|
Safety is defined as an occurrence of any adverse events during whole study period.
|
Baseline to Week 24
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Tolerability
Time Frame: Baseline to Week 24
|
Tolerability is defined as the participants who complete the current study with neither discontinuation nor being unable to increase the study drug for at least 12 weeks or longer due to any adverse event across whole study period.
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Baseline to Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Unified Multiple System Atrophy Rating Scale (UMSARS)
Time Frame: Baseline and Week 24, respectively
|
Altered level of UMSARS from baseline to week 24.
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Baseline and Week 24, respectively
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Mini Mental Status Exam (MMSE)
Time Frame: Baseline and Week 24, respectively
|
Altered level of MMSE score from baseline to week 24.
|
Baseline and Week 24, respectively
|
Montreal Cognitive Assessment (MoCA)
Time Frame: Baseline and Week 24, respectively
|
Altered level of MoCA score from baseline to week 24.
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Baseline and Week 24, respectively
|
Geriatric Depression Scale (GDS)
Time Frame: Baseline and Week 24, respectively
|
Altered level of GDS from baseline to week 24.
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Baseline and Week 24, respectively
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Pathological Conditions, Anatomical
- Autonomic Nervous System Diseases
- Primary Dysautonomias
- Hypotension
- Atrophy
- Multiple System Atrophy
- Shy-Drager Syndrome
Other Study ID Numbers
- 4-2017-0990
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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