Combination Therapy to Improve SCI Recovery.

NCT05563103 | Recruiting

• 2 other identifiers: 2022P002036W81XWH-22-1-0998
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine how combining bouts of low oxygen, transcutaneous spinal cord stimulation, and walking training may improve walking function for people with chronic spinal cord injury.

Conditions

Spinal Cord Injuries

Keywords

Walk; Rehabilitation; Strength; Movement; Spinal cord injury; low oxygen; electrical stimulation; walking training

Outcome Measures

Primary Outcomes (2)

• Change in walking recovery, assessed by 10 meter walk test (10MWT)

  Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.

  Through study completion, an average of 12 weeks

• Rate of change in walking recovery, assessed by 10 meter walk test (10MWT)

  Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Rate of change is the number of treatment sessions required to achieve an increase in 10MWT speed of at least the minimal clinically important difference (0.06 m/s) as compared to pre-treatment baseline.

  Through study completion, an average of 12 weeks

Secondary Outcomes (6)

• Change in walking recovery, assessed by 6 minute walk test (6MWT)

  Through study completion, an average of 12 weeks

• Change in walking recovery, assessed by timed up-and-go (TUG) test

  Through study completion, an average of 12 weeks

• Change in pain severity, assessed by the Numeric Pain Rating Scale (NPRS)

  Through study completion, an average of 12 weeks

• Change in cognitive function, assessed by the California Verbal Learning Test (CVLT)

  Through treatment completion, an average of 4 weeks

• Systemic hypertension incidence rate

  Through treatment completion, an average of 4 weeks

Other Outcomes (6)

• Change in lower extremity strength, assessed by American Spinal Injury Association Impairment Scale (AIS) lower extremity motor scores (LEMS)

  Through study completion, an average of 12 weeks

• Change in spasticity, assessed by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS)

  Through study completion, an average of 12 weeks

• Change in bowel dysfunction, assessed by the Neurogenic Bowel Dysfunction Score (NBDS) v2.1

  Through study completion, an average of 12 weeks

Study Arms (3)

AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)

EXPERIMENTAL

Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Other: Daily acute intermittent hypoxia; Other: Walking + tSTIM

Sham + WALKtSTIM

SHAM COMPARATOR

Sham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Other: Room air (SHAM); Other: Walking + tSTIM

AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)

SHAM COMPARATOR

Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.

Other: Daily acute intermittent hypoxia; Other: Walking + Sham transcutaneous spinal stimulation (tSHAM)

Interventions

Room air (SHAM) OTHER

Each participant will be exposed to 8 sessions of daily room air via air generators over the span of two weeks. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes of 1.5 minute normoxia (FIO2=0.21±0.02).

Sham + WALKtSTIM

Walking + tSTIM OTHER

Individuals will participate in 45 minutes of gait training while having transcutaneous spinal cord stimulation. Stimulation intensity will be 80% involuntary motor threshold.

AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM); Sham + WALKtSTIM

Daily acute intermittent hypoxia OTHER

Each participant will be exposed to 8 sessions of daily acute intermittent hypoxia via air generators over the span of two weeks. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes which include intervals of 1.5 minute hypoxia (FIO2=0.10±0.02, i.e. 10% O2) and 1 minute normoxia (FIO2=0.21±0.02).

AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM); AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)

Walking + Sham transcutaneous spinal stimulation (tSHAM) OTHER

Individuals will participate in 45 minutes of gait training while having SHAM transcutaneous spinal cord stimulation. The stimulation will briefly increase to 80% involuntary motor threshold and then brought down to 0 within 30 seconds.

AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 70 years of age
• medically stable with medical clearance from study physician to participate
• SCI at or below C2 (phrenic sparing) and at or above L2 with at least some sensory or motor function preserved below the neurologic level
• non-progressive etiology of spinal injury
• American Spinal Injury Association (ASIA) scores of C-D at initial screen
• ambulatory (able to complete the 10-meter walk test without support from another person)
• chronic injury (define as \> 12 months post-injury) to avoid potential for spontaneous neurological plasticity and recovery

You may not qualify if:

• severe concurrent illness or pain, including unhealed decubiti, severe neuropathic or chronic pain syndrome, severe infection (e.g., urinary tract), hypertension, cardiovascular disease, pulmonary disease, severe osteoporosis, active heterotopic ossification in the lower extremities, severe systemic inflammation
• \< 24 on Mini-Mental Exam
• severe recurrent autonomic dysreflexia
• history of severe cardiovascular/pulmonary complications including hypertension (systolic blood pressure \> 150 mmHg)
• pregnancy because of unknown effects of AIH or tSTIM on a fetus (individuals of childbearing potential will not otherwise be excluded)
• botulinum toxin injections in lower extremity muscles within the prior three months
• history of tendon or nerve transfer surgery in the lower extremity
• untreated severe sleep-disordered breathing characterized by uncontrolled hypoxia and sleep fractionation that may impact the outcome of this study.
• active implanted devices (e.g., intrathecal baclofen pump)
• receiving concurrent electrical stimulation
• motor threshold evoked by transcutaneous spinal stimulation \>200 mA

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead
• United States Department of Defense: collaborator
• Shirley Ryan AbilityLab: collaborator

Study Sites (2)

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

RECRUITING

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, 02138, United States

RECRUITING

Related Publications (8)

• Cutler MJ, Swift NM, Keller DM, Wasmund WL, Smith ML. Hypoxia-mediated prolonged elevation of sympathetic nerve activity after periods of intermittent hypoxic apnea. J Appl Physiol (1985). 2004 Feb;96(2):754-61. doi: 10.1152/japplphysiol.00506.2003. Epub 2003 Oct 10.

  PMID: 14555683 BACKGROUND

• Dale-Nagle EA, Hoffman MS, MacFarlane PM, Mitchell GS. Multiple pathways to long-lasting phrenic motor facilitation. Adv Exp Med Biol. 2010;669:225-30. doi: 10.1007/978-1-4419-5692-7_45.

  PMID: 20217354 BACKGROUND

• Estes S, Zarkou A, Hope JM, Suri C, Field-Fote EC. Combined Transcutaneous Spinal Stimulation and Locomotor Training to Improve Walking Function and Reduce Spasticity in Subacute Spinal Cord Injury: A Randomized Study of Clinical Feasibility and Efficacy. J Clin Med. 2021 Mar 11;10(6):1167. doi: 10.3390/jcm10061167.

  PMID: 33799508 BACKGROUND

• Gad P, Hastings S, Zhong H, Seth G, Kandhari S, Edgerton VR. Transcutaneous Spinal Neuromodulation Reorganizes Neural Networks in Patients with Cerebral Palsy. Neurotherapeutics. 2021 Jul;18(3):1953-1962. doi: 10.1007/s13311-021-01087-6. Epub 2021 Jul 9.

  PMID: 34244928 BACKGROUND

• Tan AQ, Sohn WJ, Naidu A, Trumbower RD. Daily acute intermittent hypoxia combined with walking practice enhances walking performance but not intralimb motor coordination in persons with chronic incomplete spinal cord injury. Exp Neurol. 2021 Jun;340:113669. doi: 10.1016/j.expneurol.2021.113669. Epub 2021 Feb 27.

  PMID: 33647273 BACKGROUND

• Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27.

  PMID: 24285617 BACKGROUND

• 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.

  PMID: 21821826 BACKGROUND

• Muter WM, Mansson L, Tuthill C, Aalla S, Barth S, Evans E, McKenzie K, Prokup S, Yang C, Sandhu M, Rymer WZ, Edgerton VR, Gad P, Mitchell GS, Wu SS, Shan G, Jayaraman A, Trumbower RD. A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO2ST Trial. Neurotrauma Rep. 2023 Nov 6;4(1):736-750. doi: 10.1089/neur.2023.0036. eCollection 2023.

  PMID: 38028272 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

salicylhydroxamic acid; Walking

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Locomotion; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise; Motor Activity

Study Officials

• Randy Trumbower, PT, PhD

  Harvard Medical School (HMS and HSDM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noah Piazza, BS

CONTACT

617-952-6953; npiazza2@mgb.org

Randy Trumbower, PT, PhD

CONTACT

randy.trumbower@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: October 3, 2022
• Study Start: January 17, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The study protocol and statistical analysis plan will be disseminated by December 2022. Participant data will be available at the end of the trial.
• Access Criteria: Principal investigators will be able to receive deidentified data.

Locations

US (2)