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

NCT03403309 | Completed Phase 2

• 1 other identifier: 4-2017-0990
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

A purpose of the present study is to investigate the capability of serum uric acid elevation, safety, and tolerability of inosine 5'-monophosphate in patients with multiple system atrophy with multicenter, randomized, placebo controlled, parallel assigned design. This may provide the cornerstone for future extended trial in multiple system atrophy, a debilitating disease to date.

Conditions

Multiple System Atrophy

Keywords

Multiple system atrophy; Uric acid; Inosine 5'-monophosphate; Inosine monophosphate; Inosinic acid

Outcome Measures

Primary Outcomes (3)

• Serum uric acid elevation

  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

• Safety

  Safety is defined as an occurrence of any adverse events during whole study period.

  Baseline to Week 24

• Tolerability

  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.

  Baseline to Week 24

Secondary Outcomes (4)

• Unified Multiple System Atrophy Rating Scale (UMSARS)

  Baseline and Week 24, respectively

• Mini Mental Status Exam (MMSE)

  Baseline and Week 24, respectively

• Montreal Cognitive Assessment (MoCA)

  Baseline and Week 24, respectively

• Geriatric Depression Scale (GDS)

  Baseline and Week 24, respectively

Study Arms (2)

Inosine 5'-monophosphate arm

EXPERIMENTAL

Subjects are treated with inosine 5'-monophosphate to increase serum uric acid level.

Drug: 1) Inosine 5'-monophosphate

Placebo arm

PLACEBO COMPARATOR

Subjects are treated with placebo not to increase serum uric acid level.

Drug: Placebo

Interventions

1) Inosine 5'-monophosphate DRUG

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.

Inosine 5'-monophosphate arm

Placebo DRUG

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.

Placebo arm

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Department of Neurology, Yonsei University College of Medicine

Seoul, Seou, 120-752, South Korea

Location

MeSH Terms

Conditions

Multiple System Atrophy

Interventions

Inosine Monophosphate

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Inosine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Triple-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: January 18, 2018
• Study Start: May 2, 2018
• Primary Completion: June 10, 2019
• Study Completion: June 10, 2019
• Last Updated: July 8, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)