Effects of istradefylline and low oxygen on breathing in ALS

Acute Adenosine Receptor Antagonism to Promote Breathing Plasticity in ALS

This study is testing if a medication called istradefylline, combined with short periods of low oxygen, can improve breathing in people with ALS and healthy adults.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 21 Years to 80 Years
• Sex: All
• Sponsor: University of Florida (Academic / other)
• Locations: 2 sites (Gainesville, Florida and 1 other locations)
• Trial ID: NCT05377424 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the impact of istradefylline, an adenosine 2A receptor antagonist, combined with acute intermittent hypoxia (AIH) on breathing in patients with amyotrophic lateral sclerosis (ALS) and healthy adults. Participants will undergo four study visits where they will receive different combinations of istradefylline or placebo with either AIH or sham AIH. The study aims to assess both the feasibility and efficacy of this treatment approach through a randomized, placebo-controlled design. Each visit will include a breathing test and a review of medical history to ensure participant eligibility.

Who should consider this trial

Good fit: Ideal candidates include adults aged 21-80 with a confirmed diagnosis of ALS and a vital capacity greater than 60% of the predicted value.

Not a fit: Patients with active respiratory infections, other neurodegenerative diseases, or significant cardiovascular issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve breathing function in ALS patients, potentially enhancing their quality of life.

How similar studies have performed: Previous studies have shown promising results with similar approaches, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Non-smoking adults aged 21-80 years will be eligible to participate.

   - Upon screening, eligible patients will have an
2. ALS diagnosis (El Escorial diagnostic classifications of probable/definite ALS),
3. vital capacity (VC) \> 60% of predicted value, and
4. ALS Functional Rating Scale (ALSFRS-R) scores of 2 or greater for bulbar and respiratory items: swallowing, speech, salivation, dyspnea, orthopnea, and respiratory insufficiency.
5. Additionally, patients taking riluzole and/or edaravone must be on a stable dose for \>30 days.
6. Unaffected control subjects will be eligible if they have a vital capacity (VC) \> 60% of predicted value.

Exclusion Criteria:

Patient and control are ineligible if they

1. are pregnant
2. have an active respiratory infection,
3. took antibiotics within 4 weeks,
4. are diagnosed with another neurodegenerative disease,
5. have symptomatic cardiovascular disease or dysrhythmias (resting tachycardia and hypertension),
6. exhibit history or presence of hypoxemia or hypercapnia,
7. presence of rest tachypnea (RR ˃30),
8. have a BMI \>35 kg/m2,
9. have a seizure disorder,
10. take respiratory inhalers daily for airway disease, or
11. require external respiratory support while awake and upright, or
12. supplemental oxygen at rest or at night.
13. In addition, the following conditions are exclusionary for the use of istradefylline: routine use of CYP3A4 inducers (i.e. carbamazepine, phenobarbitol, rifampin, phenytoin, St. John's Wort, glucocorticoids) or
14. medications that may suppress ventilation, history of moderate renal impairment or severe hepatic impairment, and history of hallucinations or psychosis.
15. Patients who cannot safety swallow thin liquids (required for administration of istradefylline and placebo) will also be ineligible.

Where this trial is running

Gainesville, Florida and 1 other locations

• Clinical and Translational Research Building — Gainesville, Florida, United States (Recruiting)
• UF Health Jacksonville — Jacksonville, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Barbara Smith — University of Florida
• Study coordinator: Julia Prascak, BS

Conditions ALS; hypoxia; breathing; istradefylline