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Multi-centered, placebo-controlled, double-blind, randomized clinical trial to assess the effect of oral inosine on the onset of wearing off in patients with early stage Parkinson's disease (Multi-centered, placebo-controlled, double-blind, randomized clinical trial to assess the effect of oral inosine on the onset of wearing off in patients with early stage Parkinson's disease)

Randomized clinical trial to assess the disease modifying effect of oral inosine for patients with Parkinson's disease (Randomized clinical trial to assess the disease modifying effect of oral inosine for patients with Parkinson's disease)

26

Eligibility was assessed in 39 people. Ten people were excluded per study criteria and 3 withdrew. 26 people were randomized to the inosine group or the placebo group 1:1. There were 5 men in each group. Mean age was 68.54 (7.50), 66.92 (9.00) respectively. Disease duration was longer in the inosine group (3.26 (1.70), 1.94 (1.14)) but there was no significant difference in Hoehn and Yahr stage (2.46 (0.78), 2.15 (0.38))

2015.12.01 IRB approval 2016.03.22 Enrollment begun (First participant) 2019.11.01 Enrollment completed (Last participant) 2022.03.22 Follow-up completed

Sixty-one adverse events were observed - 32 in the inosine group and 29 in the placebo group, including 3 severe adverse effects in the inosine group (1 gastric ulcer, 1 acute pyelonephritis, 1 impaired consciousness with hypoglycemia) and 1 in the placebo group (spondylolisthesis). Doctors judged these SAE were not related to the intervention. However, two AEs judged as "related to the intervention" were observed - an occurrence of a kidney stone in the inosine group and one blood in urine in the placebo group. Both resolved without treatment.

The primary endpoint was the time to development of dyskinesia, which was defined by 2 or more scores in the 19 item Wearing-off questionnaire. 6/26 and 5/26 developed dyskinesia during the 2-years of follow-up but there was no evidence that inosine slowed the development of dyskinesia. For the secondary analysis, we tested the trajectory differences between the two arms for various biomarkers for Parkinson's disease - Hoehn and Yahr Scale, MDS-UPDRS, medication dosage, and imaging biomarkers, but we could not find any significant differences between the inosine arm and the placebo arm.

Inosine was tolerable and it effectively increased the plasma level of urate but we did not observed a protective effect on the progression of Parkinson's disease

April. 26, 2022

No

NA

https://jrct.mhlw.go.jp/latest-detail/jRCTs061180060

Nagai Masahiro

Ehime University Hospital

Shitsukawa 454, Toon, Ehime

mnagai@m.ehime-u.ac.jp

Nagai Masahiro

Ehime University Hospital

Shitsukawa 454, Toon, Ehime

+81-899605095

mnagai@m.ehime-u.ac.jp

Complete

Dec. 01, 2015

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

prevention purpose

Diagnosed as having Parkinson's disease according to UK Parkinson's Disease Society Brain Bank criteria.
Confirmed negative for vascular Parkinsonism by Brain CT/MRI within one year
Within 5 years (60 months) from the start of any anti-Parkinsonism medication.
19 item-Wearing-off questionnaire <= 1 at the time of the screening visit and Visit 1.
Serum urate level <= 5.5 mg/dL in male or <= 4.2 mg/dL in female.
Age >=20 and obtained written informed consent.

A history of kidney stones, gout(or chronic arthritis), ischemic heart disease
A history of kidney failure of eGFR <= 60 at the screening visit.
Having uncontrolled hypertension which is defined as SBP>=160 or DBP >=100
Current treatment with medication which slows urate excretion, which is defined as taking diuretics, losartan, anti-tuberculosis drugs or immune-suppression agents.
Being pregnant or having an intention to become pregnant during the study period.
Other factors that investigators deem inappropriate to enroll for the trial. (e.g. Having malignancy, arthritis which is difficult to discern from gout, severe allergic history to drugs)

Both

Parkinson's disease

Inosine to maintain a serum urate level between 6.0-7.5 mg/dL for 2 years or placebo (500mg/CP)

D010300

Time between the first administration of the drug to the onset of wearing off
(19 item-Wearing-off questionnaire 2 or larger)

Time taken to reach Hoehn&Yahr 3.0 or above
Score change in UPDRS
Medication of levodopa over 450
Change in SBR in DATSCAN
Change in H/M in MIBG

+81-89-960-5172

Jan. 29, 2019

none