Amyotrophic Lateral SclerosisPhase 2SURE-ALS2NCT03168711
Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing Inosine in people with Amyotrophic Lateral Sclerosis, run by Massachusetts General Hospital at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Inosine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Oct 2017to 7 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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%.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
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
- Safety, as measured by adverse events
- 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).
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Inosine, Placebo
- Keywords
- ALS, Inosine, Uric acid, Urate, Glutathione, Biomarker, Oxidative stress, Oxidative damage
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InosineDrug
Subjects on inosine will receive 1-6 capsules a day of 500 mg inosine titrated to target urate levels of 7 - 8 mg/dL.
PlaceboDrug
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Baseline to Week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start1 Oct 2017
- Primary completion10 Dec 2019
- Study completion7 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Salah Foundation, Sean M. Healey & AMG Center for ALS
- Responsible party
- Principal investigator, Sabrina Paganoni, M.D., Massachusetts General Hospital
- Investigators
- Sabrina Paganoni, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03168711
- Sponsor's protocol ID
- SURE-ALS2
- Acronym
- SURE-ALS2
- Status last verified
- Feb 2021
- First submitted
- 24 May 2017
- Last updated
- 18 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22323210Atassi 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.
PubMed 25298304Parkinson 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.
PubMed 24366103Beukenhorst 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.
PubMed 35119373
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT03168711
- Acronym / sponsor ID
- SURE-ALS2 / SURE-ALS2
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Inosine, Uric acid, Urate, Glutathione, Biomarker, Oxidative stress, Oxidative damage
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- The Salah Foundation, Sean M. Healey & AMG Center for ALS
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 10 Dec 2019 (actual)
- Study completion
- 7 Jan 2020 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Posted 18 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Safety, as measured by adverse events
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inosine | Experimental | Drug: InosineSubjects will be administered oral inosine daily. The dose of inosine will be titrated to obtain serum urate levels of 7 - 8 mg/dL. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be administered oral placebo daily. The dose of placebo will be titrated to obtain serum urate levels of 7 - 8 mg/dL. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InosineSubjects on inosine will receive 1-6 capsules a day of 500 mg inosine titrated to target urate levels of 7 - 8 mg/dL. | Drug | Inosine |
| PlaceboSubjects 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. | Drug | Placebo |
Primary outcome
Number of Participants With 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22323210Paganoni 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.
- Background: PubMed 25298304Atassi 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.
- Background: PubMed 24366103Parkinson 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.
- Derived from this study: PubMed 35119373Beukenhorst 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabrina Paganoni, MD, PhD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inosine in people with Amyotrophic Lateral Sclerosis, run by Massachusetts General Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: Baseline to Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03168711, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2021.