Istradefylline and AIH for ALS

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Barbara Smith

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Florida

Must not be taking: CYP3A4 inducers, Ventilation suppressants

Disqualifiers: Pregnancy, Respiratory infection, Neurodegenerative, Cardiovascular, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to determine the effects of a medication, istradefylline, in conjunction with breathing air with reduced oxygen for short periods of time (called acute intermittent hypoxia, or AIH), on breathing. This project will study breathing in people with amyotrophic lateral sclerosis (ALS) and unaffected, age-matched adults. Istradefylline is prescribed to increase movement in people with other neuromuscular conditions. A recently completed study found that people with ALS took deeper breaths, 60 minutes after using AIH.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of riluzole and/or edaravone for more than 30 days if you are taking them. You cannot participate if you use certain medications like CYP3A4 inducers or those that may suppress breathing.

Research Team

Barbara Smith

Principal Investigator

University of Florida

Eligibility Criteria

Adults aged 21-75 with ALS, non-smokers, having a vital capacity over 60% of predicted value and an ALSFRS-R score above 30. They must not have used antibiotics recently or have certain respiratory or cardiovascular issues. Stable doses of riluzole/edaravone for over 30 days are required if in use.

Inclusion Criteria

My lung function is more than 60% of what is expected for someone my age and size.

I have been on a stable dose of riluzole and/or edaravone for over 30 days.

I am between 21 and 80 years old and do not smoke.

Exclusion Criteria

Individuals who took antibiotics within 4 weeks

Pregnant individuals

I currently have an active respiratory infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo 4 individual study visits with different conditions: AIH + istradefylline, sham-AIH + istradefylline, AIH + placebo, and sham-AIH + placebo.

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

Treatment Details

Interventions

• Istradefylline (Adenosine 2A Receptor Antagonist)
• Low Oxygen therapy (Other)
• Placebo counterpart to the istradefylline drug (Placebo)
• SHAM counterpart to low oxygen therapy (Placebo)

Trial Overview The trial tests the effects of a drug called istradefylline and low oxygen therapy on breathing in ALS patients compared to placebos. It aims to see if these treatments help patients take deeper breaths without causing discomfort.

Participant Groups

Group I: AIH + istradefylline (AIH+IST) Experimental Treatment 2 Interventions

Participants enrolled in this study arm will ingest a 20mg tablet containing istradefylline. Four hours later, participants will receive acute intermittent hypoxia (AIH). Breathing and pinch strength will be tested prior to taking the medication, and then immediately before, 60 minutes and 120 minutes after AIH. Participants will breathe 15 episodes/session of acute low oxygen. Air concentrations will be monitored to ensure delivery of 1-minute episodes of low oxygen, with 2 minutes room-air intervals. Respiratory rate, oxygen saturation, heart rate/rhythm, and blood pressure will be monitored throughout the session.

Group II: Sham-AIH + placebo (sham+CON) Active Control 2 Interventions

This is a sham counterpart to low oxygen, and a placebo counterpart to the istradefylline drug. Participants enrolled in this study arm will ingest a 20mg tablet containing microcrystalline cellulose. Four hours later, participants will receive SHAM acute intermittent hypoxia (SHAM). Breathing and pinch strength will be tested prior to taking the medication, and then immediately before, 60 minutes and 120 minutes after SHAM. Participants will breathe 15 episodes/session of sham low oxygen, in which normal air is used. One-minute episodes of sham low oxygen are separated by 2 minutes room-air intervals. Respiratory rate, oxygen saturation, heart rate/rhythm, and blood pressure will be monitored throughout the session.

Group III: AIH + placebo (AIH+CON) Active Control 2 Interventions

This is a placebo counterpart to the istradefylline drug. Participants enrolled in this study arm will ingest a 20mg tablet containing microcrystalline cellulose. Four hours later, participants will receive acute intermittent hypoxia (AIH). Breathing and pinch strength will be tested prior to taking the medication, and then immediately before, 60 minutes and 120 minutes after AIH. Participants will breathe 15 episodes/session of acute low oxygen. Air concentrations will be monitored to ensure delivery of 1-minute episodes of low oxygen, with 2 minutes room-air intervals. Respiratory rate, oxygen saturation, heart rate/rhythm, and blood pressure will be monitored throughout the session.

Group IV: Sham-AIH + istradefylline (sham+IST) Active Control 2 Interventions

This is a sham counterpart to the low oxygen. Participants enrolled in this study arm will ingest a 20mg tablet containing istradefylline. Four hours later, participants will receive SHAM acute intermittent hypoxia (SHAM). Breathing and pinch strength will be tested prior to taking the medication, and then immediately before, 60 minutes and 120 minutes after SHAM. Participants will breathe 15 episodes/session of sham low oxygen, in which normal air is used. One-minute episodes of sham low oxygen are separated by 2 minutes room-air intervals. Respiratory rate, oxygen saturation, heart rate/rhythm, and blood pressure will be monitored throughout the session.

Istradefylline is already approved in Japan for the following indications:

Approved in Japan as Nouriast for:

• Parkinson's disease

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Dr. Stephen J. Motew

University of Florida

Chief Executive Officer since 2024

MD cum laude from the University of Illinois at Chicago School of Medicine, Master's in Healthcare Administration from the University of North Carolina at Chapel Hill

Dr. Timothy E. Morey

University of Florida

Chief Medical Officer since 2023

MD and Bachelor's from the University of Florida

ALS Association

Collaborator

Trials

46

Recruited

17,500+