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Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS) (SURE-ALS2)

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ClinicalTrials.gov Identifier: NCT03168711
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : November 26, 2018
Sponsor:
Collaborators:
The Salah Foundation
MGH cure ALS Fund
Information provided by (Responsible Party):
Sabrina Paganoni, M.D., Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE May 24, 2017
First Posted Date  ICMJE May 30, 2017
Last Update Posted Date November 26, 2018
Actual Study Start Date  ICMJE October 1, 2017
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 25, 2017)
  • Safety Will be Assessed by the Occurrence of Adverse Events [ Time Frame: Baseline to Week 24 ]
    Safety will be assessed by the occurrence of adverse events such as kidney stones and gout (expected adverse events) in all participants receiving at least 1 dose of study drug
  • Tolerability to Complete the Entire 20 Week Study on Study Drug [ Time Frame: Baseline to Week 20 ]
    Tolerance of study drug will be defined as the number of participants who able to complete the 20-week study without permanently discontinuing study drug or suspending study drug for greater than 28 days
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03168711 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS)
Official Title  ICMJE Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS)
Brief 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 showed safety and feasibility of urate elevation in patients with ALS. The Principal Investigator is now pursuing a multi-center Phase II trial to confirm these findings with longer exposure time.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: Inosine
    Subjects on inosine will receive 1-6 capsules a day of 500 mg inosine titrated to target urate levels of 7 - 8 mg/dL.
  • Drug: Placebo
    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.
Study Arms  ICMJE
  • Experimental: Inosine
    Subjects will be administered oral inosine daily. The dose of inosine will be titrated to obtain serum urate levels of 7 - 8 mg/dL.
    Intervention: Drug: Inosine
  • Placebo Comparator: Placebo
    Subjects will be administered oral placebo daily. The dose of placebo will be titrated to obtain serum urate levels of 7 - 8 mg/dL.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 25, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03168711
Other Study ID Numbers  ICMJE SURE-ALS2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sabrina Paganoni, M.D., Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE
  • The Salah Foundation
  • MGH cure ALS Fund
Investigators  ICMJE
Principal Investigator: Sabrina Paganoni, MD, PhD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP