Effects of Remote Ischemic Conditioning on Hand Use in Individuals With SCI and ALS

NCT03851302 | Completed Results

• 2 other identifiers: HAR-18-47R03HD097709
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Rehabilitation interventions such as physical training and neural stimulation after spinal cord injury (SCI) have been shown to increase neural plasticity. However, both physical training and neural stimulation require a large number of repetitions, and the retention of the intervention effects may be fleeting. In this proposal the investigators will test Remote ischemic conditioning (RIC), which has been shown to promote neural plasticity and has practical and theoretical advantages. RIC consists of transiently restricting blood flow to any 'remote' limb using a blood pressure cuff. This induces several of the body's systemic defensive reactions. RIC has been shown to improve motor learning. The investigators propose that RIC alters motor pathway excitability through a combination of systemic increases in plasticity-promoting factors and inhibition of inflammatory factors. The investigators have designed a clinical trial to test this hypothesis in 8 persons with SCI and 8 able-bodied controls. All participants will receive active/sham RIC plus a hand exercise. The investigators will measure effects on blood pressure, motor neuron excitability, and systemic inflammatory markers before and after RIC as well as after hand exercise. Starting July 2021, we will also enroll 5 individuals with Amyotrophic lateral sclerosis (ALS) in this study.

Conditions

Spinal Cord Injuries; Amyotrophic Lateral Sclerosis

Keywords

Remote ischemic conditioning; Neuroplasticity; transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• Percent Change of Electromyographic Responses After Remote Ischemic Conditioning (RIC) Plus Hand Isometric Exercise

  Response to electrical and magnetic stimulation will be measured via peak-to-peak amplitude (millivolts) in abductor pollicis brevis muscle. Percent change of the electromyographic responses was measured immediately after active/sham RIC plus isometric hand exercise in comparison with baseline measurement. The RIC plus hand exercise duration is 60 minutes.

  Outcome measured immediately after completion of RIC plus isometric hand exercise. The RIC plus hand exercise duration is 60 minutes.

Secondary Outcomes (5)

• Percent Change of Electromyographic Responses After RIC But Before Hand Isometric Exercise

  Outcome measured immediately after completion of RIC. The RIC duration is 50 minutes.

• Percent Change of Electromyographic Responses 15 Mins After RIC Plus Hand Isometric Exercise

  Outcome measured 15 minutes after completion of RIC plus isometric hand exercise. The RIC plus hand exercise duration is 60 minutes. Therefore this is 75 minutes post baseline.

• Blood Pressure

  Mean arterial pressure at baseline and immediately after intervention on the same day. RIC plus hand exercise duration is 60 minutes.

• Heart Rate

  Heart rate at baseline and immediately after intervention on the same day. RIC plus hand exercise duration is 60 minutes.

• Oxygen Saturation

  Pulse oximetry at baseline and immediately after intervention on the same day. RIC plus hand exercise duration is 60 minutes.

Other Outcomes (1)

• Inflammatory Mediators: the Intensity of the Gene Expression of Toll-like Receptor (TLR) Signal Pathway.

  Change in mediator level between baseline measurement and immediately after completion of RIC. RIC duration is 50 minutes.

Study Arms (6)

Able bodied: Able bodied: sham first, then active

EXPERIMENTAL

Subjects without SCI or ALS. Sham first, then active.

Other: Active Remote Ischemic Conditioning; Other: Sham Remote Ischemic Conditioning; Other: Isometric hand exercise

Able bodied: active first, then sham

EXPERIMENTAL

Subjects without SCI or ALS. Active first, then sham.

Other: Active Remote Ischemic Conditioning; Other: Sham Remote Ischemic Conditioning; Other: Isometric hand exercise

Spinal Cord Injured: active first, then sham

EXPERIMENTAL

Participants with Spinal Cord Injury. Active first, then sham.

Other: Active Remote Ischemic Conditioning; Other: Sham Remote Ischemic Conditioning; Other: Isometric hand exercise

Spinal Cord Injured: sham first, then active

EXPERIMENTAL

Participants with Spinal Cord Injury. Sham first, then active.

Other: Active Remote Ischemic Conditioning; Other: Sham Remote Ischemic Conditioning; Other: Isometric hand exercise

Amyotrophic lateral sclerosis: active first, then sham.

EXPERIMENTAL

Participants with amyotrophic lateral sclerosis. Active first, then sham.

Other: Active Remote Ischemic Conditioning; Other: Sham Remote Ischemic Conditioning; Other: Isometric hand exercise

Amyotrophic lateral sclerosis: sham first, then active.

EXPERIMENTAL

Participants with amyotrophic lateral sclerosis. Sham first, then active.

Other: Active Remote Ischemic Conditioning; Other: Sham Remote Ischemic Conditioning; Other: Isometric hand exercise

Interventions

Active Remote Ischemic Conditioning OTHER

The active RIC protocol involves 5 cycles of 5-min inflation and 5-min deflation on the non-target arm. The active RIC will be achieved via blood pressure cuff inflation to 200 mmHg.

Able bodied: Able bodied: sham first, then active; Able bodied: active first, then sham; Amyotrophic lateral sclerosis: active first, then sham.; Amyotrophic lateral sclerosis: sham first, then active.; Spinal Cord Injured: active first, then sham; Spinal Cord Injured: sham first, then active

Sham Remote Ischemic Conditioning OTHER

The sham RIC protocol involves 5 cycles of 5-min inflation and 5-min deflation on the non-target arm. The sham RIC will be achieved via blood pressure cuff inflation to 10 mmHg below the subjects' diastolic blood pressure which would not cause the blood occlusion.

Able bodied: Able bodied: sham first, then active; Able bodied: active first, then sham; Amyotrophic lateral sclerosis: active first, then sham.; Amyotrophic lateral sclerosis: sham first, then active.; Spinal Cord Injured: active first, then sham; Spinal Cord Injured: sham first, then active

Isometric hand exercise OTHER

Participants will be instructed to pinch a dynamometer with thumb and index finger at different intensities and durations. The intensities of pinch force will be 10%, 25%, and 50% of the maximal voluntary contraction (MVC). For each intensity, durations of 2, 4, and 6 s will be employed, which resulted in nine different combinations delivered in pseudorandom order. Participants will perform 2 sets of the isometric hand exercise (18 pinches in total). The interval between each pinch will be 2 seconds, with 30 second intervals between each set.

Able bodied: Able bodied: sham first, then active; Able bodied: active first, then sham; Amyotrophic lateral sclerosis: active first, then sham.; Amyotrophic lateral sclerosis: sham first, then active.; Spinal Cord Injured: active first, then sham; Spinal Cord Injured: sham first, then active

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years;
• Chronic (more than 12 months since injury) motor-incomplete SCI between neurological levels C2-C8
• Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to median nerve stimulation;
• Detectable motor evoked potentials in left or right APB muscles to transcranial magnetic stimulation;
• Able to perform thumb-middle finger opposition pinch task with detectable APB EMG muscle activity.
• ALS participants
• Age between 21 and 75 years;
• Diagnosis of probable or definite ALS.
• Incomplete weakness of left or right wrist or hand muscles: score of 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction.
• Detectable motor evoked potentials in left or right APB muscles to transcranial magnetic stimulation;
• Able to perform thumb-middle finger opposition pinch task with detectable APB electromyography (EMG) muscle activity.

You may not qualify if:

• Multiple spinal cord lesions;
• History of seizures;
• Use of medications that significantly lower seizure threshold, such as amphetamines and bupropion;
• History of implanted brain/spine/nerve stimulators, aneurysm clips, or cardiac pacemaker/defibrillator;
• Any extremity soft tissue, orthopedic, or vascular condition or injury that may contraindicate remote limb ischemic conditioning (RLIC) (uncontrolled hypertension, peripheral vascular disease, hematological disease, severe hepatic or renal dysfunction);
• Any other contraindication to undergoing magnetic resonance imaging (except for claustrophobia);
• Clinically significant infection of any kind (urinary tract, pulmonary, skin or other)
• Significant coronary artery or cardiac conduction disease;
• Open skin lesions over the neck, shoulders, or arms;
• Pregnancy
• Unsuitable for study participation as determined by study physician. In addition, a medical record review will be conducted to identify any other medical concerns that might increase the risks associated with participation.

Sponsors & Collaborators

• Bronx VA Medical Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

James J. Peters VA Medical Center

The Bronx, New York, 10468, United States

Location

Related Publications (1)

• Wu YK, Harel NY, Wecht JM, Bloom OE. Effects of Remote Ischemic Conditioning on Hand Engagement in individuals with Spinal cord Injury (RICHES): protocol for a pilot crossover study. F1000Res. 2021 Jun 10;10:464. doi: 10.12688/f1000research.52670.2. eCollection 2021.

  PMID: 35342620 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Principal Investigator
• Organization: Bronx Veterans Medical Research Foundation

NOAM.HAREL@VA.GOV

718-584-9000 x1742

Study Officials

• Yu-Kuang Wu, PT, PhD

  James J. Peters VA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 16, 2019
• First Posted: February 22, 2019
• Study Start: October 28, 2019
• Primary Completion: July 30, 2022
• Study Completion: October 31, 2022
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Available now once above stipulations met.
• Access Criteria: Available now once above stipulations met.

Locations

US (1)