A Pilot Study of Inosine in Amyotrophic Lateral Sclerosis (ALS)

NCT02288091 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 701
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open label, 12-week study of inosine treatment. Inosine treatment leads to an increase in the levels of urate (uric acid) in the blood. The primary objective of the study is to determine the tolerability of oral administration of inosine. Secondary study objectives include the measurement of biomarkers of oxidative stress and damage in response to inosine treatment.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Inosine; Uric acid; Urate; Glutathione; Biomarker; Oxidative stress; Oxidative damage; proof-of-concept

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Adverse Events

  Safety will be assessed by the occurrence of adverse events.

  12 weeks

• Tolerability to Complete the Entire 12 Week Study on Study Drug.

  Tolerability will be defined as the ability of subjects to complete the entire 12-week study on study drug.

  12 weeks

Secondary Outcomes (3)

• Blood Biomarkers (GSH) at Baseline and Week 12

  12 weeks

• Neuroimaging Biomarkers at Baseline and Week 12

  12 weeks

• Blood Biomarkers (FRAP) at Baseline and Week 12

  12 weeks

Study Arms (1)

Open-label

EXPERIMENTAL

Subjects will receive oral inosine daily.

Drug: Inosine

Interventions

Inosine DRUG

Twenty-five eligible subjects will receive inosine for 12 weeks (administered in the form of 500 mg capsules, 1 to 6 capsules a day for a total daily dose of up to 3 gm). The dose of inosine will be titrated to target urate levels of 7-8 mg/dL based on urate level measurement that will occur at Week 2, Week 4, Week 6, and Week 9 after Baseline.

Open-label

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older.
• Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
• 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).
• Willingness to undergo magnetic resonance spectroscopy (MRS) at Baseline and at Week 12 of the study.
• 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.

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).
• Urate crystalluria at Screening.
• 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).
• Contraindications to undergo magnetic resonance spectroscopy (MRS) at Baseline and at Week 12 of the study such as history of claustrophobia, inability to lie flat for approximately one hour, or metal implants (metal pins or plates, extensive non-removable dental work, cerebral aneurysm clips, pacemaker).
• 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 PI judgment, or a history of active substance abuse within the prior year.
• Anything that, in the opinion of the 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.

Sponsors & Collaborators

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

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• 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

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: Sabrina Paganoni, MD, PhD
• 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: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 5, 2014
• First Posted: November 11, 2014
• Study Start: January 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: November 6, 2017
• Results First Posted: October 2, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)