Adenosine 2A Receptor (A2AR) Antagonism and AIH in ALS Study

About the study

Researchers at the University of Florida are testing a therapeutic strategy to delay breathing problems in those with ALS. This strategy combines an FDA-approved drug known as Istradefylline with a breathing intervention called acute intermittent hypoxia, or AIH.

What is AIH?

Acute intermittent hypoxia (AIH) consists of brief exposures to air you would find at higher altitudes, interspersed with periods of normal air. Imagine traveling up to Mt. Denali for 1 minute, then back to Florida for 2 minutes. That is what AIH is like. Studies have shown AIH can be delivered safely and seems to assist with rehabilitation.

Is AIH safe?

According to studies in other neurological disease, AIH is not taxing and barely detectable. AIH has been studied for the past 20 years and has not been associated with any adverse events.

What is Istradefylline?

Istradefylline is a medication approved to increase movement in people with Parkinson’s disease. It acts to block a site in the nervous system (A2A receptor). Some early studies have shown that Istradefylline may help increase and prolong the effects of AIH on muscle strength.

What does involvement in this study look like?

To assess eligibility, participants will visit the Clinical and Translational Building on the University of Florida campus for 1 short screening visit. Upon signing the informed consent form, the study team will conduct the rest of the screening visit procedures, which include:

  • A medical history questionnaire
  • Breathing test
  • 12-lead ECG test to measure electrical activity of your heart. The study team will place small stickers (called electrodes) on your chest, arms and legs for a 5-10 minute test.
  • At-home sleep study

Once a subject is determined to be eligible by the principal investigator and medical director of this study, subjects will participate in 4 study visits about 2 weeks apart. Sessions will last the majority of the workday (9am-5pm). Study visits include multiple breaks to rest, a private patient room with a bed and reclining chair, and light lunch.

Each of the 4 sessions will include randomization of either AIH or Sham (fake AIH intervention), combined with either Istradefylline or placebo (“sugar pill”). Blood tests, breathing, and strength measures will be taken at each study visit. Research is always voluntary, so the subject can decide at any time if they choose to withdraw from the study. Up to $500 reimbursement will be available upon completion of study. Additionally, there is a chance you might be eligible for up to $250 of reimbursement for travel expenses.

Eligibility Criteria

  • Non-smoking adults aged 21-75 years
  • ALS diagnosis
  • Vital Capacity (VC) >/= 60% of predicted value
  • Unaffected control subjects will be eligible if they have a VC >/= 60% of predicted value
  • ALS Functional Rating Scale (ALSFRS-R) score >/= 30
  • Not using supplemental oxygen
  • Not using a breathing machine while awake and upright
  • Other eligibility criteria will be assessed at the screening visit

Study Location

The screening visit will take place at the Clinical Translational Research Building (CTRB) located on the University of Florida’s campus. The address is 2004 Mowry Road Gainesville, FL 32610. 

Participants should park in the garage directly next to the building in one of the spaces located on the first floor designated for research participants. After parking, you can access the CTRB through a side door that faces the garage. Once you walk through the doors, you will arrive at a reception desk where you can check in and get a parking pass. The study team will also be notified.

The University of Florida Clinical and Translational Research Building serves as the headquarters for clinical and translational science at UF and in the state. The building houses patient-oriented research venues for the Institute on Aging and the Clinical and Translational Science Institute.

Contact Information

Study Coordinator: Juliette Clavier;; (352) 273-6855

Principal Investigator: Barbara Smith, PhD, PT;

Principal Investigator


Barbara Smith, PhD, PT

Dr. Barbara Smith is a Research Assistant Professor in the Department of Physical Therapy at the University of Florida. She teaches in the Physiology and Exercise Science track of the entry-level Doctor of Physical Therapy program. Dr. Smith completed her PhD in Rehabilitation Science as a T32 Scholar at University of Florida. Her research interests are the control of breathing in conditions of health and disease, and harnessing rehabilitation and regenerative therapies to restore ventilation in cases of injury or neuromuscular disease.