Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS)

Study Purpose:

This is a multi-center, 20-week study of inosine treatment.

Study Objectives and Endpoints The primary objective of the study is to determine the safety and tolerability of oral administration of inosine (administered daily) dosed to moderately elevate serum urate over 20 weeks.

The primary outcome measures will be

1. Safety, as measured by adverse events

2. Tolerability, defined as the ability of subjects to complete the entire 20-week study.

As an exploratory objective, we will test the feasibility and utility of a smartphone application for monitoring symptoms and disease progression in patients with amyotrophic lateral sclerosis (ALS).

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis

Study Type:


Type of Intervention:


Intervention Name:

Inosine, Placebo




Phase 2

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

Sabrina Paganoni, MD, PhD, Massachusetts General Hospital ID:


Neals Affiliated?


Coordinating Center Contact Information

Massachusetts General Hospital

Boston, Massachusetts, 02114 United States

Full Study Summary:

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease for which there is no cure. 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.

The Principal Investigator has recently concluded a Pilot Study of Inosine in ALS, which was a short, open label, single center study involving 25 subjects [NCT02288091]. The study assessed safety and feasibility of urate elevation in patients with ALS. The Principal Investigator is now pursuing a multi-center Phase II trial to assess the findings of the open label study with longer exposure time.

Study Sponsor:

Massachusetts General Hospital

Participant Duration:

20 weeks

Estimated Enrollment:


Estimated Study Start Date:

10 / 01 / 2017

Estimated Study Completion Date:

01 / 07 / 2020

Posting Last Modified Date:

02 / 18 / 2021

Date Study Added to

05 / 30 / 2017

Minimum Age:

18 Years

Maximum Age:

85 Years

Can participants use Riluzole?


Inclusion Criteria:

1. Age 18-85.

2. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).

3. Slow vital capacity (SVC) ≥ 60% of predicted for age, height, and gender at the Screening Visit.

4. Capable of providing informed consent and following trial procedures.

5. Serum urate < 5.5 mg/dL at screening (i.e. below the population median serum urate levels).

6. Women must not be able to become pregnant (e.g. post menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and 3 months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal (patch or contraceptive ring, for example) contraception), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.

7. Is able and willing to participate in the Mobile app study procedures.

Exclusion Criteria:

1. History of urolithiasis.

2. Urine pH < 5.5 at screening (as acidic urine is a major determinant of uric acid urolithiasis).

3. History of gout.

4. History of stroke or myocardial infarction.

5. History of symptomatic coronary artery disease (e.g. angina pectoris) or symptomatic peripheral arterial disease within 1 year prior to Screening.

6. Symptomatic congestive heart failure with a documented ejection fraction below 45%.

7. Poorly controlled arterial hypertension (SBP>160mmHg or DBP>100mmHg at Screening).

8. Women who are pregnant or lactating.

9. The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to Site Investigator judgment, or a history of active substance abuse within the prior year.

10. Anything that, in the opinion of the Site Investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.

11. Use of the following within 30 days prior to Screening: inosine, allopurinol, probenecid, more than 300mg vitamin C daily (note that a subject may take a standard multivitamin up to one tablet or capsule daily). Use of thiazides is permissible as long as the subject is on a stable dose from 1 week prior to Screening.

12. Known hypersensitivity or intolerability to inosine.

13. Renal insufficiency as defined by eGFR < 60 mL/min/1.73m2 at the time of screening.

Holy Cross Hospital

Fort Lauderdale, Florida 33308
United States

Massachusetts General Hospital

Boston, Massachusetts 02114
United States

University of Minnesota

Minneapolis, Minnesota 55455
United States