ALSPhase 1/2NCT05377424
Adenosine 2A Receptor Antagonism and AIH in ALS
A Phase 1/2 study testing Consume 20mg of istradefylline and Low Oxygen therapy in people with ALS, run by University of Florida at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- ALS
- What is being tested?
- Consume 20mg of istradefylline and Low Oxygen therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Jun 2022to 31 Aug 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Non-smoking adults aged 21-80 years will be eligible to participate.
- Upon screening, eligible patients will have an
- ALS diagnosis (El Escorial diagnostic classifications of probable/definite ALS),
- vital capacity (VC) > 60% of predicted value, and
- ALS Functional Rating Scale (ALSFRS-R) scores of 2 or greater for bulbar and respiratory items: swallowing, speech, salivation, dyspnea, orthopnea, and respiratory insufficiency.
- Additionally, patients taking riluzole and/or edaravone must be on a stable dose for >30 days.
- Unaffected control subjects will be eligible if they have a vital capacity (VC) > 60% of predicted value.
Who cannot join
- Patient and control are ineligible if they
- are pregnant
- have an active respiratory infection,
- took antibiotics within 4 weeks,
- are diagnosed with another neurodegenerative disease,
- have symptomatic cardiovascular disease or dysrhythmias (resting tachycardia and hypertension),
Show all 16Show fewer
- exhibit history or presence of hypoxemia or hypercapnia,
- presence of rest tachypnea (RR ˃30),
- have a BMI >35 kg/m2,
- have a seizure disorder,
- take respiratory inhalers daily for airway disease, or
- require external respiratory support while awake and upright, or
- supplemental oxygen at rest or at night.
- 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
- medications that may suppress ventilation, history of moderate renal impairment or severe hepatic impairment, and history of hallucinations or psychosis.
- Patients who cannot safety swallow thin liquids (required for administration of istradefylline and placebo) will also be ineligible.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinical and Translational Research Building
Gainesville, Florida, 32610
UF Health Jacksonville
Jacksonville, Florida, 32209
About this study
Official title: Acute Adenosine Receptor Antagonism to Promote Breathing Plasticity in ALS
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.
Read the detailed description
This repeated measures, placebo-controlled, randomized study will study feasibility and efficacy of istradefylline, an adenosine 2A receptor antagonist in conjunction with acute intermittent hypoxia (AIH).
Participation in this study includes a screening for eligibility, plus 4 individual study visits separated by 1 week. The eligibility screening will include a review of medical history and medications, along with a breathing test and sleep study.
Each participant will experience a different study condition on each of their 4 study visits: an "AIH + istradefylline" (AIH+IST) visit, and a "sham-AIH + istradefylline" (sham+IST) visit, an "AIH + placebo (AIH+CON)" visit, and a "sham-AIH + placebo" (sham+CON) visit. The visits will be in random order for each subject. Participants and the testing investigators will not be told which order the visits will be. Participants need to avoid exercise and caffeine and nicotine products for >8 hours before each study visit.
AIH + istradefylline visit: participants will take 20 mg of istradefylline. After a 4-hour break, participants will receive a 45-minute session of AIH, consisting of 15, one-minute periods of low oxygen (10% O2) with two-minute periods of normal oxygen (21% O2).
Sham AIH + istradefylline visit: participants will take 20 mg of istradefylline. After a 4-hour break, participants will receive a 45-minute session of SHAM AIH, consisting of 15, one-minute intervals of normal oxygen (21% O2) with two-minute periods of normal oxygen (21% O2).
AIH + placebo visit: participants will take 20 mg of microcrystalline cellulose. After a 4-hour break, participants will receive a 45-minute session of AIH, consisting of 15, one-minute periods of low oxygen (10% O2) with two-minute periods of normal oxygen (21% O2).
Sham AIH + placebo visit: participants will take 20 mg of microcrystalline cellulose. After a 4-hour break, participants will receive a 45-minute session of SHAM AIH, consisting of 15, one-minute intervals of normal oxygen (21% O2) with two-minute periods of normal oxygen (21% O2).
Venous blood samples will be collected at the start of each visit as general safety labs (complete blood count, uric acid, blood chemistry), and to assess levels of istradefylline levels in the blood. Additional blood tests 4 and 6 hours later will measure changes in serum istradefylline.
The study will assess vital signs, patient-reported symptoms, resting breathing, strength of the breathing muscles, and maximal voluntary pinch force at the start of each visit. These measures will then be repeated 1 and 2 hours after AIH or SHAM. Throughout the AIH and SHAM interventions, respiratory rate, oxygen saturation, end-tidal carbon dioxide (CO2), heart rate, and blood pressure will be monitored.
For the primary efficacy endpoint, the study will measure breath volume at the start of each visit, and 1 and 2 hours after the AIH and SHAM interventions. A linear mixed model will be used to compare differences in tidal volume. Main effects include treatment and time, with participants as random effects.
- Conditions
- ALS
- Being tested
- Consume 20mg of istradefylline, Low Oxygen therapy, Placebo counterpart to the istradefylline drug, SHAM counterpart to low oxygen therapy.
- Keywords
- ALS, hypoxia, breathing, istradefylline
- Medical subject headings
- Hypoxia, Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Consume 20mg of istradefyllineDrug
Also called Nourianz
Consume a single 20 mg istradefylline tablet
Low Oxygen therapyOther
Also called Acute Intermittent Hypoxia, AIH
Breathing short periods of low oxygen, consisting of 15 episodes of 1 minute of breathing 10% oxygen, with 2 minutes of breathing 21% oxygen. 45 minutes total.
Placebo counterpart to the istradefylline drugDrug
Also called Placebo
Consume a single microcrystalline cellulose
SHAM counterpart to low oxygen therapy.Other
Also called SHAM acute intermittent hypoxia, SHAM-AIH
Breathing short periods of sham low oxygen, consisting of 15 episodes of 1 minute of breathing 21% oxygen, separated by 2 minutes of breathing 21% oxygen. 45 minutes total.
| Study group | Role | What they receive |
|---|---|---|
| AIH + istradefylline (AIH+IST) | Experimental | 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. Receives: Drug: Consume 20mg of istradefylline; Other: Low Oxygen therapy |
| Sham-AIH + istradefylline (sham+IST) | Active comparator | 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. Receives: Drug: Consume 20mg of istradefylline; Other: SHAM counterpart to low oxygen therapy. |
| AIH + placebo (AIH+CON) | Active comparator | 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. Receives: Other: Low Oxygen therapy; Drug: Placebo counterpart to the istradefylline drug |
| Sham-AIH + placebo (sham+CON) | Active comparator | 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. Receives: Drug: Placebo counterpart to the istradefylline drug; Other: SHAM counterpart to low oxygen therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment differences in the rate of adverse events.
Any reported adverse events will be tracked and recorded.
Measured: Through study completion (an average of 4-6 weeks)
Change in resting tidal volume
Averaged volume of breaths at rest
Measured: 120 minutes after AIH
Secondary outcomes (4)
Serum Istradefylline
Blood test to measure change in level of istradefylline
Measured: 4 hours post- istradefylline or placebo
Serum Istradefylline
Blood test to measure change in level of istradefylline
Measured: 6 hours post- istradefylline or placebo
Subject-reported involuntary movements
Participants will use a 0-10 scale to report the intensity of any involuntary movements or tremors. (a higher number would correspond to more involuntary movements or tremors)
Measured: 4 hours post- istradefylline or placebo
Change in minute ventilation
Change in the average volume of air during a minute of resting breathing.
Measured: 120 minutes post-intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start21 Jun 2022
- Primary completion26 Jan 2026
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for ALSStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- ALS Association
- Responsible party
- Sponsor
- Investigators
- Barbara Smith, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05377424
- Sponsor's protocol ID
- IRB202101568
- Other IDs
- OCR41682
- Status last verified
- Feb 2026
- First submitted
- 26 Apr 2022
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5.
PubMed 21821826Vivodtzev I, Tan AQ, Hermann M, Jayaraman A, Stahl V, Rymer WZ, Mitchell GS, Hayes HB, Trumbower RD. Mild to Moderate Sleep Apnea Is Linked to Hypoxia-induced Motor Recovery after Spinal Cord Injury. Am J Respir Crit Care Med. 2020 Sep 15;202(6):887-890. doi: 10.1164/rccm.202002-0245LE. No abstract available.
PubMed 32369393Seven YB, Simon AK, Sajjadi E, Zwick A, Satriotomo I, Mitchell GS. Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition. Exp Neurol. 2020 Jan;323:113067. doi: 10.1016/j.expneurol.2019.113067. Epub 2019 Oct 17.
PubMed 31629857Sajjadi E, Seven YB, Ehrbar JG, Wymer JP, Mitchell GS, Smith BK. Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study. Exp Neurol. 2022 Jan;347:113890. doi: 10.1016/j.expneurol.2021.113890. Epub 2021 Oct 6.
PubMed 34624328Sales de Campos P, Smith-Hublou M, Olsen WL, Souza Leite W, Wymer JP, Napoli NJ, Vose AK, Pulley MT, Mitchell GS, Smith BK. Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial. JMIR Res Protoc. 2025 Nov 7;14:e76105. doi: 10.2196/76105.
PubMed 41202295
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Adenosine Receptor Antagonism to Promote Breathing Plasticity in ALS
- ClinicalTrials.gov ID
- NCT05377424
- Acronym / sponsor ID
- IRB202101568
- Conditions
- ALS
- Keywords
- ALS, hypoxia, breathing, istradefylline
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- ALS Association
- Study start
- 21 Jun 2022 (actual)
- Primary completion
- 26 Jan 2026 (actual)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 17 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This repeated measures, placebo-controlled, randomized study will study feasibility and efficacy of istradefylline, an adenosine 2A receptor antagonist in conjunction with acute intermittent hypoxia (AIH).
Participation in this study includes a screening for eligibility, plus 4 individual study visits separated by 1 week. The eligibility screening will include a review of medical history and medications, along with a breathing test and sleep study.
Each participant will experience a different study condition on each of their 4 study visits: an "AIH + istradefylline" (AIH+IST) visit, and a "sham-AIH + istradefylline" (sham+IST) visit, an "AIH + placebo (AIH+CON)" visit, and a "sham-AIH + placebo" (sham+CON) visit. The visits will be in random order for each subject. Participants and the testing investigators will not be told which order the visits will be. Participants need to avoid exercise and caffeine and nicotine products for >8 hours before each study visit.
AIH + istradefylline visit: participants will take 20 mg of istradefylline. After a 4-hour break, participants will receive a 45-minute session of AIH, consisting of 15, one-minute periods of low oxygen (10% O2) with two-minute periods of normal oxygen (21% O2).
Sham AIH + istradefylline visit: participants will take 20 mg of istradefylline. After a 4-hour break, participants will receive a 45-minute session of SHAM AIH, consisting of 15, one-minute intervals of normal oxygen (21% O2) with two-minute periods of normal oxygen (21% O2).
AIH + placebo visit: participants will take 20 mg of microcrystalline cellulose. After a 4-hour break, participants will receive a 45-minute session of AIH, consisting of 15, one-minute periods of low oxygen (10% O2) with two-minute periods of normal oxygen (21% O2).
Sham AIH + placebo visit: participants will take 20 mg of microcrystalline cellulose. After a 4-hour break, participants will receive a 45-minute session of SHAM AIH, consisting of 15, one-minute intervals of normal oxygen (21% O2) with two-minute periods of normal oxygen (21% O2).
Venous blood samples will be collected at the start of each visit as general safety labs (complete blood count, uric acid, blood chemistry), and to assess levels of istradefylline levels in the blood. Additional blood tests 4 and 6 hours later will measure changes in serum istradefylline.
The study will assess vital signs, patient-reported symptoms, resting breathing, strength of the breathing muscles, and maximal voluntary pinch force at the start of each visit. These measures will then be repeated 1 and 2 hours after AIH or SHAM. Throughout the AIH and SHAM interventions, respiratory rate, oxygen saturation, end-tidal carbon dioxide (CO2), heart rate, and blood pressure will be monitored.
For the primary efficacy endpoint, the study will measure breath volume at the start of each visit, and 1 and 2 hours after the AIH and SHAM interventions. A linear mixed model will be used to compare differences in tidal volume. Main effects include treatment and time, with participants as random effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AIH + istradefylline (AIH+IST) | Experimental | Drug: Consume 20mg of istradefylline, Other: Low Oxygen therapyParticipants 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. |
| Sham-AIH + istradefylline (sham+IST) | Active comparator | Drug: Consume 20mg of istradefylline, Other: SHAM counterpart to low oxygen therapy.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. |
| AIH + placebo (AIH+CON) | Active comparator | Other: Low Oxygen therapy, Drug: Placebo counterpart to the istradefylline drugThis 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. |
| Sham-AIH + placebo (sham+CON) | Active comparator | Drug: Placebo counterpart to the istradefylline drug, Other: SHAM counterpart to low oxygen therapy.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. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Non-smoking adults aged 21-80 years will be eligible to participate.
- ALS diagnosis (El Escorial diagnostic classifications of probable/definite ALS),
- vital capacity (VC) > 60% of predicted value, and
- ALS Functional Rating Scale (ALSFRS-R) scores of 2 or greater for bulbar and respiratory items: swallowing, speech, salivation, dyspnea, orthopnea, and respiratory insufficiency.
- Additionally, patients taking riluzole and/or edaravone must be on a stable dose for >30 days.
Key exclusion criteria (16 listed)
- Patient and control are ineligible if they
- are pregnant
- have an active respiratory infection,
- took antibiotics within 4 weeks,
- are diagnosed with another neurodegenerative disease,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Consume 20mg of istradefyllineAlso: NourianzConsume a single 20 mg istradefylline tablet | Drug | AIH + istradefylline (AIH+IST), Sham-AIH + istradefylline (sham+IST) |
| Low Oxygen therapyAlso: Acute Intermittent Hypoxia, AIHBreathing short periods of low oxygen, consisting of 15 episodes of 1 minute of breathing 10% oxygen, with 2 minutes of breathing 21% oxygen. 45 minutes total. | Other | AIH + istradefylline (AIH+IST), AIH + placebo (AIH+CON) |
| Placebo counterpart to the istradefylline drugAlso: PlaceboConsume a single microcrystalline cellulose | Drug | AIH + placebo (AIH+CON), Sham-AIH + placebo (sham+CON) |
| SHAM counterpart to low oxygen therapy.Also: SHAM acute intermittent hypoxia, SHAM-AIHBreathing short periods of sham low oxygen, consisting of 15 episodes of 1 minute of breathing 21% oxygen, separated by 2 minutes of breathing 21% oxygen. 45 minutes total. | Other | Sham-AIH + istradefylline (sham+IST), Sham-AIH + placebo (sham+CON) |
Primary outcome
Treatment differences in the rate of adverse events.
Time frame: Through study completion (an average of 4-6 weeks)
Any reported adverse events will be tracked and recorded.
Change in resting tidal volume
Time frame: 120 minutes after AIH
Averaged volume of breaths at rest
4 secondary outcomes
Serum Istradefylline
Time frame: 4 hours post- istradefylline or placebo
Serum Istradefylline
Time frame: 6 hours post- istradefylline or placebo
Subject-reported involuntary movements
Time frame: 4 hours post- istradefylline or placebo
Change in minute ventilation
Time frame: 120 minutes post-intervention.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Background: PubMed 21821826Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5.
- Background: PubMed 32369393Vivodtzev I, Tan AQ, Hermann M, Jayaraman A, Stahl V, Rymer WZ, Mitchell GS, Hayes HB, Trumbower RD. Mild to Moderate Sleep Apnea Is Linked to Hypoxia-induced Motor Recovery after Spinal Cord Injury. Am J Respir Crit Care Med. 2020 Sep 15;202(6):887-890. doi: 10.1164/rccm.202002-0245LE. No abstract available.
- Background: PubMed 31629857Seven YB, Simon AK, Sajjadi E, Zwick A, Satriotomo I, Mitchell GS. Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition. Exp Neurol. 2020 Jan;323:113067. doi: 10.1016/j.expneurol.2019.113067. Epub 2019 Oct 17.
- Background: PubMed 34624328Sajjadi E, Seven YB, Ehrbar JG, Wymer JP, Mitchell GS, Smith BK. Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study. Exp Neurol. 2022 Jan;347:113890. doi: 10.1016/j.expneurol.2021.113890. Epub 2021 Oct 6.
- Derived from this study: PubMed 41202295Sales de Campos P, Smith-Hublou M, Olsen WL, Souza Leite W, Wymer JP, Napoli NJ, Vose AK, Pulley MT, Mitchell GS, Smith BK. Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial. JMIR Res Protoc. 2025 Nov 7;14:e76105. doi: 10.2196/76105.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara Smith principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Consume 20mg of istradefylline and Low Oxygen therapy in people with ALS, run by University of Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment differences in the rate of adverse events. (time frame: Through study completion (an average of 4-6 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05377424, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.