A Pilot Study of Inosine in ALS

Study Purpose:

The purpose of this study is to evaluate the safety of inosine in volunteers with ALS.


Amyotrophic Lateral Sclerosis (ALS)

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Not enrolling


Phase I

Study Chair(s)/Principal Investigator(s):

Sabrina Paganoni, MD, PhD (Massachusetts General Hospital)

Clinicaltrials.gov ID (11 digit #):


Neals Affiliated?


Coordinating Center Contact Information

Massachusetts General Hospital
Daniela Grasso / .(JavaScript must be enabled to view this email address) / 617-726-0842
.(JavaScript must be enabled to view this email address) 165 Cambridge Street
Boston, Massachusetts 02114 United States

Full Study Summary:

Multiple lines of evidence have implicated oxidative stress in the pathophysiology of ALS. Urate (uric acid) is an endogenous antioxidant system, and urate may serve as a major defense against oxidative stress. Urate has emerged as a promising neuro-protectant and therapeutic target based on convergent epidemiological, laboratory, and clinical data in multiple neurodegenerative diseases, most notably Parkinson's disease (PD). In PD, urate elevation has been pursued as a potential therapy by administration of inosine, a urate precursor that is available as an over-the-counter supplement. Administration of inosine results in a predictable elevation of urate levels and has been shown to be safe and well tolerated in PD.

Analysis of ALS databases revealed that higher urate levels are an independent predictor of slower progression and prolonged survival in ALS. However, whether elevating urate in people with ALS would result in better outcomes is unknown. As a first step towards development of inosine as a potential treatment for ALS, in this study we will test whether inosine administration in ALS is safe and correlates with changes in the levels of biomarkers of oxidative stress and damage (as biomarkers of the intended biological effect).

The primary outcome measures will be safety, as measured by adverse events and clinically meaningful changes in vital signs, physical examination, and standard clinical laboratory tests, and tolerability, defined as the ability of subjects to complete the entire 12-week study.
The secondary objective of the study is to quantify the effect of the treatment on biomarkers of oxidative damage and stress.
An exploratory objective of the study is to measure whether changes in these biomarkers are different in people with bulbar-onset ALS compared to people with limb-onset ALS.

This study will be conducted in people who meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. At screening, eligible individuals must be at least 18 years old and must provide written informed consent prior to screening. Subjects on a stable dose of riluzole and those not taking riluzole, and women of child-bearing age at screening are eligible for inclusion as long as they meet specific protocol requirements.

Study participants will be administered oral inosine daily. The dose of inosine will be titrated to obtain serum urate levels of 7 - 8 mg/dL.
Study participants will remain on treatment until the Week 12 visit. Each participant will also have a Week 16 Follow-up Telephone Interview to assess for adverse events (AEs), changes in concomitant medications and to administer the ALSFRS-R.

Study Sponsor:

The Salah Foundation; MGH Cure ALS fund

Participant Duration:

12 weeks on drug, up to 19 weeks total including screening and follow-up phone call

Estimated Enrollment:


Estimated Study Start Date:


Estimated Study Completion Date:


Posting Last Modified Date:


Date Study Added to alsconsortium.org: