Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair

B2848-R

Contusive cervical spinal cord injury (cSCI) impairs upper limb function (reach-and-grasp) which limits daily-life activities and thus decreases the quality of life. Promoting neuroplasticity may support upper limb recovery after SCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined with motor training promotes recovery of motor function after SCI; however, the overall effects of rAIH/training are limited. The investigators will use an adult rat model of long-term contusive cSCI to study novel approaches to enhance the effect of rAIH/training on forelimb function and study the neuronal substrate underlying the effects. The findings will be used to direct the development of more effective rAIH/training approaches for people with contusive, functionally incomplete, cSCI. Because deficits in upper limb function are a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, this work may also be relevant for patients with other types of central nervous system (CNS) lesions.

2020-02-25

2025-02-10

2025-02-10

Recruiting

Early phase I

90

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

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'repetitive intermittent hypoxia treatment combined with exercise and/or NMDA agonist', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'participants and some research personnel will be blinded', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 90, 'type': 'ESTIMATED'}}

2024-02-15