- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03780829
AIH for Spinal Cord Repair
Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The overall goal is to develop effective, clinically applicable, approaches to restore upper limb function (reach-and-grasp) after chronic contusive cervical spinal cord injury (cSCI). Impairments in upper limb function significantly reduce the quality of life for people with cSCI. Reach-and-grasp actions in animals and humans are largely controlled by the corticospinal tract (CST). The investigators argue that promoting plasticity within the CST may support the recovery of upper limb function after cSCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined with motor training is a safe, minimally invasive, treatment that elicits neuroplasticity resulting in improved recovery after cSCI, but its overall effects remain limited. The main goals are to: 1) enhance rAIH/training-induced aftereffects on forelimb function and increase the understanding of the neuronal substrates in an adult rat model of chronic contusive cSCI, and 2) use this knowledge to guide the development of more effective rAIH/training approaches to improve upper limb function in humans with chronic contusive cSCI.
In Specific Aim 1, using an adult rat model of chronic contusive cSCI, the investigators will investigate the effects of rAIH frequency and dose on rAIH/training-mediated functional recovery of the impaired forelimb. Also, the investigators will combine rAIH/training with N-methyl-D-aspartate receptor (NMDA)-mediated synaptic plasticity through D-cycloserine treatment and study the effects on recovery of forelimb function. Immunocytochemistry with imaging techniques will be used to assess structural neuronal plasticity in the CST after rAIH/training. In Specific Aim 2, in people with chronic incomplete cSCI, guided by the findings in Specific Aim 1, the investigators will study the effects of rAIH frequency and concurrent D-cycloserine treatment on rAIH/training-mediated upper limb function recovery. The investigators will comprehensively analyze the effects of rAIH on the strength of electrophysiological and functional aftereffects in the upper limb.
The proposed research will provide new knowledge on rAIH/training-mediated functional and anatomical aftereffects (Specific Aim 1), which will be used to develop effective rAIH/training protocols for people with contusive, functionally incomplete, cSCI (Specific Aim 2). The data from the investigators' experiments may lead to clinically applicable approaches that improve arm and hand function recovery after chronic contusive cSCI, which would positively impact the quality of life of Veterans with cSCI. The relevance of this proposal is emphasized by the limited efficacy of current strategies to improve upper limb function after cSCI.
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Monica A Perez, PhD
- Phone Number: (312) 238-2886
- Email: mperez04@sralab.org
Study Contact Backup
- Name: Martin Oudega, PhD
- Phone Number: (305) 575-7000
- Email: moudega@sralab.org
Study Locations
-
-
Illinois
-
Hines, Illinois, United States, 60141-3030
- Recruiting
- Edward Hines Jr. VA Hospital, Hines, IL
-
Principal Investigator:
- Martin Oudega, PhD
-
Contact:
- Meghan Morrow, BA
- Phone Number: 312-238-7794
- Email: Meghan.Morrow@va.gov
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male and females Veterans between 18-85 years
- Chronic cSCI (1 yr of injury)
- Cervical injury at C8 or above
- Sensory function: impaired (score of 1) but not absent (score of 0) or intact (score of 2) innervations in dermatomes C6, C7 and C8 during light touch and pin prick stimulus using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) sensory scores
- Motor function: Able to grasp small objects with one hand and able to perform a visible precision grasp between the index finger and thumb
Motor scores ISNCSCI: 1 to 4 but not 5 on finger flexors and finger abductors on the hand tested.
- These criteria were selected to ensure that hand impairment will not interfere with the ability to perform training and proposed tests
Inclusion criteria for controls:
- Male and females (18-80 years)
- Right handed
- Able to complete precision and power grips
Exclusion Criteria:
- Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
- Any debilitating disease prior to the SCI that caused exercise intolerance
- Premorbid, ongoing major depression or psychosis, altered cognitive status
- History of head injury or stroke
- Metal plate in skull
- History of seizures
Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs
- chlorpromazine
- clozapine
- or tricyclic antidepressants
- Pregnant females
- Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease as spinal stenosis, spina bifida or herniated cervical disk
AIH Exclusion Criteria (in addition to the above listed exclusion criteria):
- resting heart rate > 120 bpm
- resting systolic blood pressure >180 mmHg
- resting diastolic blood pressure >100 mmHg
- self-reported history of unstable angina or myocardial infarction within the previous month
- resting SpO2 > or equal to 95%
- cardiopulmonary complications such as COPD
Exclusion criteria for healthy controls:
- Same as for SCI individuals
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: hypoxia plus training
combined hypoxia treatment with exercise training
|
intermittent cycles of normoxia-hypoxia
bimanual massed practice training
|
Sham Comparator: sham hypoxia plus training
combined sham hypoxia treatment with exercise training
|
bimanual massed practice training
intermittent cycles of sham hypoxia
|
Experimental: hypoxia plus training plus NMDA agonist
combined hypoxia treatment with exercise training and with NMDA agonist treatment
|
intermittent cycles of normoxia-hypoxia
bimanual massed practice training
NMDA agonist treatment
Other Names:
|
Placebo Comparator: hypoxia plus training plus sham NMDA agonist
combined hypoxia treatment with exercise training and with sham NMDA agonist treatment
|
intermittent cycles of normoxia-hypoxia
bimanual massed practice training
sham-NMDA agonist treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in grip strength
Time Frame: baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
|
Grip strength will be measured using a hand-held dynamometer, with an average force (measured in dynes) taken over the course of three trials.
A rest break is provided between trials.
Strength testing will be completed bilaterally.
|
baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
|
Change in pinch strength
Time Frame: baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
|
Pinch strength will be assessed using a digital pinch gauge (unit of Force= Newton).
The minimum value of zero will be assigned when a participant cannot actively squeeze the pinch meter between the thumb and index finger.
The mean value of total of 3 trials will be assessed, with a rest break provided between trials.
|
baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
|
Change in motor evoked potential size
Time Frame: 30 minutes before and 30 minutes after intervention
|
Resting and active motor thresholds (RMT and AMT) will be tested in each of the muscles using a stimulator.
|
30 minutes before and 30 minutes after intervention
|
Collaborators and Investigators
Investigators
- Principal Investigator: Martin Oudega, PhD, Edward Hines Jr. VA Hospital, Hines, IL
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- B2848-R
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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