Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS)
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Inosine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects on inosine will receive 1-6 capsules a day of 500 mg inosine titrated to target urate levels of 7 - 8 mg/dL.; Subjects on placebo will receive 1-6 capsules a day of 500 mg placebo (sugar pill) titrated to target urate levels of 7 - 8 mg/dL.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ALS; Inosine; Uric acid; Urate; Glutathione; Biomarker; Oxidative stress; Oxidative damage