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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
Sponsor:
Collaborators:
The Salah Foundation
MGH cure ALS Fund
Information provided by (Responsible Party):
Sabrina Paganoni, M.D., Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Amyotrophic Lateral Sclerosis
Intervention Drug: Inosine
Enrollment 32
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Open-label
Hide Arm/Group Description

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.

Period Title: Overall Study
Started 32
Randomized/Treated 25
Completed 24
Not Completed 8
Reason Not Completed
Lost to Follow-up             1
Screen fail             7
Arm/Group Title Open-label
Hide Arm/Group Description

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 Number of Baseline Participants 25
Hide Baseline Analysis Population Description
32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants
61.2  (8.4)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
18
  72.0%
Male
7
  28.0%
[1]
Measure Analysis Population Description: 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Hispanic or Latino
1
   4.0%
Not Hispanic or Latino
24
  96.0%
Unknown or Not Reported
0
   0.0%
[1]
Measure Analysis Population Description: 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   4.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   4.0%
White
23
  92.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
[1]
Measure Analysis Population Description: 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 25 participants
25
[1]
Measure Analysis Population Description: 32 subjects were consented, however, 25 patients were randomized/treated to received the study drug.
1.Primary Outcome
Title Number of Participants Experiencing Adverse Events
Hide Description Safety will be assessed by the occurrence of adverse events.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Open-label
Hide Arm/Group Description:

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 Number of Participants Analyzed 25
Measure Type: Count of Participants
Unit of Measure: Participants
22
  88.0%
2.Primary Outcome
Title Tolerability to Complete the Entire 12 Week Study on Study Drug.
Hide Description Tolerability will be defined as the ability of subjects to complete the entire 12-week study on study drug.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Twenty-four (24) out of twenty-five (25) participants completed 12 weeks of study drug treatment.
Arm/Group Title Open-label
Hide Arm/Group Description:

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 Number of Participants Analyzed 25
Measure Type: Count of Participants
Unit of Measure: Participants
24
  96.0%
3.Secondary Outcome
Title Blood Biomarkers (GSH) at Baseline and Week 12
Hide Description 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).
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Open-label
Hide Arm/Group Description:

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 Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: ƥM
Glutathione at Baseline Number Analyzed 23 participants
94.0  (28.4)
Glutathione at Week 12 Number Analyzed 20 participants
84.5  (42.6)
4.Secondary Outcome
Title Neuroimaging Biomarkers at Baseline and Week 12
Hide Description 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.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Open-label
Hide Arm/Group Description:

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 Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: mM
Motor Cortex Precentral Gyri (Baseline) Number Analyzed 20 participants
0.424  (0.064)
Motor Cortex Precentral Gyri (Week 12) Number Analyzed 18 participants
0.392  (0.064)
5.Secondary Outcome
Title Blood Biomarkers (FRAP) at Baseline and Week 12
Hide Description 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).
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Open-label
Hide Arm/Group Description:

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 Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: µM
Ferric Reducing Antioxidant Power (Baseline) Number Analyzed 24 participants
765.7  (155.1)
Ferric Reducing Antioxidant Power (Week 12) Number Analyzed 21 participants
1188.3  (294.1)
Time Frame Adverse events were collected from the time the subject signed consent until 28 days after a subject's last dose of study drug.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Open-label
Hide Arm/Group Description

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.

All-Cause Mortality
Open-label
Affected / at Risk (%)
Total   1/25 (4.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Open-label
Affected / at Risk (%) # Events
Total   3/25 (12.00%)    
Infections and infestations   
Abdominal Abscess  1  1/25 (4.00%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/25 (4.00%)  1
Respiratory Failure  1  1/25 (4.00%)  1
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Open-label
Affected / at Risk (%) # Events
Total   22/25 (88.00%)    
Gastrointestinal disorders   
Constipation  1  2/25 (8.00%)  2
Dysphagia aggravated  1  2/25 (8.00%)  2
General disorders   
Fatigue  1  2/25 (8.00%)  2
Weakness worsened  1  3/25 (12.00%)  3
Injury, poisoning and procedural complications   
Ankle sprain  1  2/25 (8.00%)  2
Fall  1  8/25 (32.00%)  11
Investigations   
Weight Loss  1  4/25 (16.00%)  4
Metabolism and nutrition disorders   
Decreased appetite  1  2/25 (8.00%)  2
Musculoskeletal and connective tissue disorders   
Weakness of arms  1  2/25 (8.00%)  2
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sabrina Paganoni, MD, PhD
Organization: Massachusetts General Hospital
Phone: 617-724-3914
EMail: spaganoni@mgh.harvard.edu
Layout table for additonal information
Responsible Party: Sabrina Paganoni, M.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02288091     History of Changes
Other Study ID Numbers: 701
First Submitted: November 5, 2014
First Posted: November 11, 2014
Results First Submitted: February 8, 2017
Results First Posted: October 2, 2017
Last Update Posted: November 6, 2017