Trial Outcomes & Findings for A Pilot Study of Inosine in Amyotrophic Lateral Sclerosis (ALS) (NCT NCT02288091)

NCT ID: NCT02288091

Last Updated: 2017-11-06

Results Overview

Safety will be assessed by the occurrence of adverse events.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 32 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2017-11-06

Participant Flow

Participant milestones

Measure	Open-label Subjects will receive oral inosine daily. Inosine: 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.
Overall Study STARTED	32
Overall Study Randomized/Treated	25
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure	Open-label Subjects will receive oral inosine daily. Inosine: 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.
Overall Study Lost to Follow-up	1
Overall Study Screen fail	7

Baseline Characteristics

32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.

Baseline characteristics by cohort

Measure	Open-label n=25 Participants Subjects will receive oral inosine daily. Inosine: 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.
Age, Continuous	61.2 years STANDARD_DEVIATION 8.4 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Sex: Female, Male Male	7 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB) Asian	1 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB) White	23 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Region of Enrollment United States	25 participants n=5 Participants • 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.

PRIMARY outcome

Timeframe: 12 weeks

Population: No expected adverse events of special interest, such as kidney stones and gout, occurred during the course of the study. However, twenty-two (22) out of twenty-five (25) participants did experience an adverse event during the course of the study.

Safety will be assessed by the occurrence of adverse events.

Outcome measures

Measure

Open-label n=25 Participants Subjects will receive oral inosine daily. Inosine: 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

22 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Twenty-four (24) out of twenty-five (25) participants completed 12 weeks of study drug treatment.

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

Outcome measures

Measure

Open-label n=25 Participants Subjects will receive oral inosine daily. Inosine: 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.

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

24 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Two (2) subjects did not have blood drawn for GSH analysis at the Baseline Visit. Five (5) subjects did not have blood drawn for GSH analysis at the Week 12 visit. These missing samples are due to technical issues, such as a difficult blood draw or issue with sample processing.

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).

Outcome measures

Measure	Open-label n=23 Participants Subjects will receive oral inosine daily. Inosine: 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.
Blood Biomarkers (GSH) at Baseline and Week 12 Glutathione at Baseline	94.0 ƥM Standard Deviation 28.4
Blood Biomarkers (GSH) at Baseline and Week 12 Glutathione at Week 12	84.5 ƥM Standard Deviation 42.6

SECONDARY outcome

Timeframe: 12 weeks

Population: Five (5) subjects did not have a MRS done at the Baseline and Week 12 visits. Of the 20 that had a baseline MRS, 2 patients did not have a Week 12 MRS done. These missing MRS scans are due to technical difficulties, such as subjects were unable to complete the scan.

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.

Outcome measures

Measure	Open-label n=20 Participants Subjects will receive oral inosine daily. Inosine: 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.
Neuroimaging Biomarkers at Baseline and Week 12 Motor Cortex Precentral Gyri (Baseline)	0.424 mM Standard Deviation 0.064
Neuroimaging Biomarkers at Baseline and Week 12 Motor Cortex Precentral Gyri (Week 12)	0.392 mM Standard Deviation 0.064

SECONDARY outcome

Timeframe: 12 weeks

Population: One (1) subject did not have blood drawn for FRAP analysis at the Baseline Visit. Four (4) subjects did not have blood drawn for FRAP analysis at the Week 12 visit. These missing samples are due to technical issues, such as a difficult blood draw or issue with sample processing.

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).

Outcome measures

Measure	Open-label n=24 Participants Subjects will receive oral inosine daily. Inosine: 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.
Blood Biomarkers (FRAP) at Baseline and Week 12 Ferric Reducing Antioxidant Power (Week 12)	1188.3 µM Standard Deviation 294.1
Blood Biomarkers (FRAP) at Baseline and Week 12 Ferric Reducing Antioxidant Power (Baseline)	765.7 µM Standard Deviation 155.1

Adverse Events

Open-label

Serious events: 3 serious events

Other events: 22 other events

Deaths: 1 deaths

Serious adverse events

Measure	Open-label n=25 participants at risk Subjects will receive oral inosine daily. Inosine: 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.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.0% 1/25 • Number of events 1 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Infections and infestations Abdominal Abscess	4.0% 1/25 • Number of events 1 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	4.0% 1/25 • Number of events 1 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.

Other adverse events

Measure	Open-label n=25 participants at risk Subjects will receive oral inosine daily. Inosine: 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.
Investigations Weight Loss	16.0% 4/25 • Number of events 4 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Gastrointestinal disorders Constipation	8.0% 2/25 • Number of events 2 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Gastrointestinal disorders Dysphagia aggravated	8.0% 2/25 • Number of events 2 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
General disorders Fatigue	8.0% 2/25 • Number of events 2 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
General disorders Weakness worsened	12.0% 3/25 • Number of events 3 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Injury, poisoning and procedural complications Ankle sprain	8.0% 2/25 • Number of events 2 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Injury, poisoning and procedural complications Fall	32.0% 8/25 • Number of events 11 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Metabolism and nutrition disorders Decreased appetite	8.0% 2/25 • Number of events 2 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Musculoskeletal and connective tissue disorders Weakness of arms	8.0% 2/25 • Number of events 2 • Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.

Additional Information

Sabrina Paganoni, MD, PhD

Massachusetts General Hospital

Phone: 617-724-3914

Email: spaganoni@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place