Istradefylline + Low Oxygen Therapy for Spinal Cord Injury

Overseen By William Muter

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Randy Trumbower, PT, PhD

Must not be taking: Caffeine, NSAIDs

Disqualifiers: Cardiovascular disease, Diabetes, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment for spinal cord injury patients that combines breathing low oxygen air with a medication. The goal is to improve walking by strengthening nerve pathways and blocking certain brain effects that could reduce this benefit. Breathing low-oxygen air has shown potential in enhancing walking recovery in spinal cord injury patients by promoting neuroplasticity.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have allergies or intolerances to caffeine or NSAIDs, you may not be eligible to participate.

What data supports the effectiveness of the treatment Istradefylline + Low Oxygen Therapy for Spinal Cord Injury?

Research shows that daily intermittent low oxygen therapy can improve walking speed and endurance in people with chronic spinal cord injury, suggesting potential benefits for recovery. However, there is no direct evidence for the effectiveness of Istradefylline in this context. ^{1 2 3 4 5}

How is the treatment of Istradefylline + Low Oxygen Therapy unique for spinal cord injury?

This treatment combines Istradefylline, a drug that may have neuroprotective effects, with Low Oxygen Therapy, which can promote recovery by enhancing the brain's ability to adapt and reorganize itself. This combination is unique because it targets both neuroprotection and neuroplasticity, potentially offering a novel approach to improving outcomes after spinal cord injury. ^{2 5 6 7 8}

Research Team

Randy Trumbower, PT, PhD

Principal Investigator

Spaulding Rehabilitation Hospital

Eligibility Criteria

This trial is for adults aged 18-75 with a spinal cord injury that happened over a year ago. They must be able to move their legs voluntarily and take one step without help. The injury should be between the C2 and T12 levels of the spine, not getting worse over time. People with diabetes, severe illnesses, allergies to caffeine or NSAIDs, pregnant women, or those with seizure disorders can't join.

Inclusion Criteria

I am between 18 and 75 years old.

Medical clearance to participate

You had a significant injury more than 12 months ago.

Exclusion Criteria

I do not have any severe illnesses like heart disease or unhealed wounds.

You are allergic to caffeine or non-steroidal anti-inflammatory drugs (NSAIDs), or these substances make you feel unwell.

I have diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combinatorial intervention of istradefylline or placebo with low oxygen therapy or SHAM therapy for 4 weeks

4 weeks

4 sessions per week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of walking speed and distance

3 weeks

Treatment Details

Interventions

• Istradefylline
• Low Oxygen Therapy

Trial Overview The study tests if low oxygen therapy (LOT) combined with an adenosine A2a receptor blocker called Istradefylline improves walking in people after spinal cord injuries. LOT may boost nerve pathway strength but could be less effective due to increased adenosine; this trial checks if blocking adenosine helps recovery.

Participant Groups

Group I: Istradefylline+low oxygen training Experimental Treatment 2 Interventions

Drug: Nourianz Other Names: KW6002, Istradefylline Participants enrolled in this study arm will ingest a 20mg tablet/day containing istradefylline starting 14 days prior to the first low oxygen therapy and continuing for 14 additional days. Participants will consume a total of 28 istradefylline tablets. Other: low oxygen training Other Names: therapeutic intermittent hypoxia, acute intermittent hypoxia Participants will breathe 15 episodes/session of acute low oxygen via an automated air generator system (4 sessions/week x 2 weeks). During the 90-second episodes of low oxygen, air concentrations will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) with 60-second room-air intervals (FIO2 0.21±0.02). Throughout experimentation, blood pressure, respiratory rate, and heart rate will be monitored. We also will assess for changes in sleep quality and pain level.

Group II: Placebo+low oxygen training Active Control 1 Intervention

This is a placebo counterpart to the istradefylline drug. Participants enrolled in this study arm will ingest a 20mg placebo tablet/day containing dextrose starting 14 days prior to the first low oxygen therapy (LOT) and continuing for 14 additional days. Participants will consume a total of 28 placebo tablets. Other: low oxygen training Other Names: therapeutic intermittent hypoxia, acute intermittent hypoxia Participants will breathe 15 episodes/session of acute low oxygen via an automated air generator system (4 sessions/week x 2 weeks). During the 90-second episodes of low oxygen, air concentrations will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) with 60-second room-air intervals (FIO2 0.21±0.02). Throughout experimentation, blood pressure, respiratory rate, and heart rate will be monitored. We also will assess for changes in sleep quality and pain level.

Group III: Istradefylline+SHAM Active Control 1 Intervention

Drug: Nourianz Other Names: KW6002, Istradefylline This is a SHAM counterpart to low oxygen therapy. Participants enrolled in this study arm will ingest a 20mg tablet/day containing istradefylline starting 14 days prior to the first SHAM therapy and continuing for 14 additional days. Participants will consume a total of 28 istradefylline tablets. Participants will breathe 15 episodes/session of SHAM via an automated air generator system (4 sessions/week x 2 weeks). The system will fill reservoir bags attached to a non-rebreathing face mask. During the 90-second episodes of SHAM, air concentrations will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia) with 60-second room-air intervals (FIO2 0.21±0.02). Throughout experimentation, blood pressure, respiratory rate, and heart rate will be monitored. We also will assess for changes in sleep quality and pain level.

Istradefylline is already approved in United States, Japan for the following indications:

Approved in United States as Nourianz for:

• Parkinson's disease

Approved in Japan as Nouriast for:

• Parkinson's disease

Who Is Running the Clinical Trial?

Randy Trumbower, PT, PhD

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

Daily acute intermittent hypoxia (dAIH) significantly improved walking speed and endurance in individuals with chronic incomplete spinal cord injury, as shown by measurable improvements in the 10-Meter and 6-Minute Walk Tests after just one day of treatment.

Combining dAIH with overground walking further enhanced these benefits, indicating that this combination therapy could be a more effective approach for improving mobility in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Hayes, HB., Jayaraman, A., Herrmann, M., et al.[2022]

In a study of 2040 individuals with spinal cord injury, a total of 775 unique medications were administered within the first 60 days post-injury, highlighting a significant prevalence of polypharmacy, with some patients taking up to 43 medications per day.

The findings suggest that the high number of medications, including those given for prophylactic reasons, could potentially influence neurological recovery, emphasizing the need for careful management of pharmacological treatments in acute spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological management of acute spinal cord injury: a longitudinal multi-cohort observational study. Jutzeler, CR., Bourguignon, L., Tong, B., et al.[2023]

This pilot study aims to assess the safety and feasibility of administering oral glyburide to 10 patients with acute cervical spinal cord injury within 8 hours of injury, building on preclinical evidence that glyburide can reduce secondary injury effects like progressive hemorrhagic necrosis.

Glyburide is considered a promising neuroprotective strategy due to its potential to mitigate secondary injury mechanisms, despite the risk of hypoglycemia, making it an interesting addition to standard care for spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SCING-Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA. Minnema, AJ., Mehta, A., Boling, WW., et al.[2020]

Acute intermittent hypoxia (AIH) is a safe and effective therapy that can enhance strength, walking speed, endurance, and dynamic balance in individuals with chronic, incomplete spinal cord injury (SCI).

AIH shows promise for promoting walking recovery through neuroplasticity mechanisms, but more research is needed to determine its effectiveness across larger groups and to identify optimal treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions. Tan, AQ., Barth, S., Trumbower, RD.[2022]

Acute intermittent hypoxia (AIH) combined with task-specific training (TST) can significantly enhance motor function recovery after spinal cord injuries, suggesting a promising therapeutic approach.

The study proposes a hypothetical model to explain how AIH and TST work together at the neural and cellular levels, aiming to guide future experiments that could optimize their combined neurotherapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergy between Acute Intermittent Hypoxia and Task-Specific Training. Welch, JF., Sutor, TW., Vose, AK., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Sequential changes of hypoxia-inducible factor 1 alpha in experimental spinal cord injury and its significance. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacological management of acute spinal cord injury: a longitudinal multi-cohort observational study. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Management of Hypotension and Bradycardia Caused By Spinal Cord Injury. The Usefulness of Midodrine and Methylxanthines. [2020]

5. England pubmed.ncbi.nlm.nih.gov

SCING-Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Prednisolone Pretreatment Enhances Intermittent Hypoxia-Induced Plasticity in Persons With Chronic Incomplete Spinal Cord Injury. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Synergy between Acute Intermittent Hypoxia and Task-Specific Training. [2022]