Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS)

NCT03168711 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SURE-ALS2
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

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. 1.Safety, as measured by adverse events
2. 2.Tolerability, defined as the ability of subjects to complete the entire 20-week study.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Inosine; Uric acid; Urate; Glutathione; Biomarker; Oxidative stress; Oxidative damage

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  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

  Baseline to Week 24

• Tolerability to Complete the Entire 20 Week Study on Study Drug

  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

  Baseline to Week 20

Study Arms (2)

Inosine

EXPERIMENTAL

Subjects will be administered oral inosine daily. The dose of inosine will be titrated to obtain serum urate levels of 7 - 8 mg/dL.

Drug: Inosine

Placebo

PLACEBO COMPARATOR

Subjects will be administered oral placebo daily. The dose of placebo will be titrated to obtain serum urate levels of 7 - 8 mg/dL.

Drug: Placebo

Interventions

Inosine DRUG

Subjects on inosine will receive 1-6 capsules a day of 500 mg inosine titrated to target urate levels of 7 - 8 mg/dL.

Inosine

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-85.
• Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
• Slow vital capacity (SVC) ≥ 60% of predicted for age, height, and gender at the Screening Visit.
• Capable of providing informed consent and following trial procedures.
• Serum urate \< 5.5 mg/dL at screening (i.e. below the population median serum urate levels).
• 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.
• Is able and willing to participate in the Mobile app study procedures.

You may not qualify if:

• History of urolithiasis.
• Urine pH \< 5.5 at screening (as acidic urine is a major determinant of uric acid urolithiasis).
• History of gout.
• History of stroke or myocardial infarction.
• History of symptomatic coronary artery disease (e.g. angina pectoris) or symptomatic peripheral arterial disease within 1 year prior to Screening.
• Symptomatic congestive heart failure with a documented ejection fraction below 45%.
• Poorly controlled arterial hypertension (SBP\>160mmHg or DBP\>100mmHg at Screening).
• Women who are pregnant or lactating.
• 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.
• 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.
• 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.
• Known hypersensitivity or intolerability to inosine.
• Renal insufficiency as defined by eGFR \< 60 mL/min/1.73m2 at the time of screening.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• The Salah Foundation: collaborator
• Sean M. Healey & AMG Center for ALS: collaborator

Study Sites (3)

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (4)

• Paganoni S, Zhang M, Quiroz Zarate A, Jaffa M, Yu H, Cudkowicz ME, Wills AM. Uric acid levels predict survival in men with amyotrophic lateral sclerosis. J Neurol. 2012 Sep;259(9):1923-8. doi: 10.1007/s00415-012-6440-7. Epub 2012 Feb 10.

  PMID: 22323210 BACKGROUND

• Atassi N, Berry J, Shui A, Zach N, Sherman A, Sinani E, Walker J, Katsovskiy I, Schoenfeld D, Cudkowicz M, Leitner M. The PRO-ACT database: design, initial analyses, and predictive features. Neurology. 2014 Nov 4;83(19):1719-25. doi: 10.1212/WNL.0000000000000951. Epub 2014 Oct 8.

  PMID: 25298304 BACKGROUND

• Parkinson Study Group SURE-PD Investigators; Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, Curhan GC, Hare JM, Hooper DC, Kieburtz KD, Macklin EA, Oakes D, Rudolph A, Shoulson I, Tennis MK, Espay AJ, Gartner M, Hung A, Bwala G, Lenehan R, Encarnacion E, Ainslie M, Castillo R, Togasaki D, Barles G, Friedman JH, Niles L, Carter JH, Murray M, Goetz CG, Jaglin J, Ahmed A, Russell DS, Cotto C, Goudreau JL, Russell D, Parashos SA, Ede P, Saint-Hilaire MH, Thomas CA, James R, Stacy MA, Johnson J, Gauger L, Antonelle de Marcaida J, Thurlow S, Isaacson SH, Carvajal L, Rao J, Cook M, Hope-Porche C, McClurg L, Grasso DL, Logan R, Orme C, Ross T, Brocht AF, Constantinescu R, Sharma S, Venuto C, Weber J, Eaton K. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol. 2014 Feb;71(2):141-50. doi: 10.1001/jamaneurol.2013.5528.

  PMID: 24366103 BACKGROUND

• Beukenhorst AL, Burke KM, Scheier Z, Miller TM, Paganoni S, Keegan M, Collins E, Connaghan KP, Tay A, Chan J, Berry JD, Onnela JP. Using Smartphones to Reduce Research Burden in a Neurodegenerative Population and Assessing Participant Adherence: A Randomized Clinical Trial and Two Observational Studies. JMIR Mhealth Uhealth. 2022 Feb 4;10(2):e31877. doi: 10.2196/31877.

  PMID: 35119373 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Inosine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Sabrina Paganoni
• Organization: Massachusetts General Hospital

spaganoni@mgh.harvard.edu

617-724-3914

Study Officials

• Sabrina Paganoni, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: May 30, 2017
• Study Start: October 1, 2017
• Primary Completion: December 10, 2019
• Study Completion: January 7, 2020
• Last Updated: February 18, 2021
• Results First Posted: February 18, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)