A Pilot Study of Inosine in Amyotrophic Lateral Sclerosis (ALS)
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|ClinicalTrials.gov Identifier: NCT02288091|
Recruitment Status : Completed
First Posted : November 11, 2014
Results First Posted : October 2, 2017
Last Update Posted : November 6, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: Inosine||Phase 1|
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. As a first step towards development of inosine as a potential treatment for ALS, in this study we will test whether inosine administration in ALS is safe and correlates with changes in the levels of biomarkers of oxidative stress and damage (as biomarkers of the intended biological effect).
The primary outcome measures will be safety, as measured by adverse events and clinically meaningful changes in vital signs, physical examination, and standard clinical laboratory tests, and tolerability, defined as the ability of subjects to complete the entire 12-week study.
The secondary objective of the study is to quantify the effect of the treatment on biomarkers of oxidative damage and stress.
An exploratory objective of the study is to measure whether changes in these biomarkers are different in people with bulbar-onset ALS compared to people with limb-onset ALS.
This study will be conducted in people who meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. At screening, eligible individuals must be at least 18 years old and must provide written informed consent prior to screening. Subjects on a stable dose of riluzole and those not taking riluzole, and women of child-bearing age at screening are eligible for inclusion as long as they meet specific protocol requirements.
Study participants will be administered oral inosine daily. The dose of inosine will be titrated to obtain serum urate levels of 7 - 8 mg/dL.
Study participants will remain on treatment until the Week 12 visit. Each participant will also have a Week 16 Follow-up Telephone Interview to assess for adverse events (AEs), changes in concomitant medications and to administer the ALSFRS-R.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Inosine in Amyotrophic Lateral Sclerosis (ALS)|
|Study Start Date :||January 2015|
|Actual Primary Completion Date :||March 2016|
|Actual Study Completion Date :||March 2016|
Subjects will receive oral inosine daily.
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.
- Number of Participants Experiencing Adverse Events [ Time Frame: 12 weeks ]Safety will be assessed by the occurrence of adverse events.
- Tolerability to Complete the Entire 12 Week Study on Study Drug. [ Time Frame: 12 weeks ]Tolerability will be defined as the ability of subjects to complete the entire 12-week study on study drug.
- Blood Biomarkers (GSH) at Baseline and Week 12 [ Time Frame: 12 weeks ]Blood samples will be obtained at baseline and after 12 weeks of treatment to measure biomarkers of oxidative stress and damage such as glutathione (GSH).
- Neuroimaging Biomarkers at Baseline and Week 12 [ Time Frame: 12 weeks ]Magnetic resonance spectroscopy (MRS) will be performed to measure the levels of glutathione in the motor cortex; levels of glutathione at Week 12 (post-treatment) will be compared to pre-treatment levels.
- Blood Biomarkers (FRAP) at Baseline and Week 12 [ Time Frame: 12 weeks ]Blood samples will be obtained at baseline and after 12 weeks of treatment to measure biomarkers of oxidative stress and damage such as ferric reducing antioxidant power (FRAP).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02288091
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Sabrina Paganoni, MD, PhD||Massachusetts General Hospital|