Hybrid-FES Exercise to Prevent Cardiovascular Declines in Acute SCI

• Sponsor: Spaulding Rehabilitation Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02139436
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 68
• Location: 1
• Arms: 3
• Duration (Months): 87
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Each year, 11,000 people suffer a spinal cord injury (SCI) in the U.S. Within the first year, there are profound declines in physiologic function, forming the underlying substrate for future cardiovascular disease . In fact, acquired cardiovascular disease is an increasingly recognized consequence of SCI and is the leading cause of death in SCI. Though incompletely understood, the almost 10-fold prevalence of cardiovascular disease results in part from profound physiologic 'detraining' resulting from motor impairment and immobility. Currently, effective interventions preventing acute declines that lead to cardiovascular compromise and increased risk in SCI are lacking - exercise therapy for those with SCI is challenging and when employed, is typically limited to the upper body. Recently, the investigators refined a unique form of exercise for those with SCI that specifically mirrors exercise performed by those without SCI. Functional Electrical Stimulation (FES) Row Training (RT) couples volitional arm and electrically controlled leg exercise, resulting in a hemodynamic profile that produces the beneficial cardiac loading conditions of large muscle mass exercise. As such, FES-RT may be a safe and effective way to attenuate cardiovascular declines following SCI. The investigators aims are to test the overall hypotheses that FES-RT will: 1) mitigate against increased visceral adiposity and reduced insulin sensitivity, 2) prevent worsening lipid profile and compromised baroreflex function, and 3) counter ventricular wall thickening and declining ventricular function occurring with acute SCI, and that these effects will be greater than that observed with an arms-only exercise group. Changes with FES-RT will be compared to a time (wait-list) control and to arms-only-RT. Individuals with an SCI within the last 3-6 months will be randomized to FES-RT, to a time control, or arms-only-RT. Measures will be made at baseline and 6 months. The investigators work will provide results that clearly delineate potential health benefits of FES-RT, and if FES-RT is effective in a majority of those with SCI, its application, implementation, and integration could be easily replicated.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injury	Other: FES-row-training; Other: Arms-only-row training; Other: Time Control	N/A

Detailed Description

We will enroll approximately 60 individuals within three to six months post SCI to obtain data on 50 individuals. One-half of the subjects (N=25) will be randomized to immediately enroll in 6 months of FES-RT. One third (N=18) will be randomized to a wait-list to provide time control data from baseline to 6 months. A wait-list control group is routine in exercise studies because most volunteers are interested in participating in an exercise program. Hence, time controls are difficult to capture since many of those randomized to receive no exercise either drop from the study entirely, or end up pursuing some form of exercise on their own. Therefore, a vehicle for enrollment of a time control group that is acceptable to most volunteers is a wait-list. Therefore, a six month time control will provide data on expected declines and then subjects will be randomized to six months exercise.

Training Protocols for Each Study Group

1. FES-RT GROUP

Subjects will begin with short intervals of FES-RT interspersed with rest intervals and/or arms-only rowing intervals depending on fitness level and the response to the FES. A maximum FES-rowing test will be performed at baseline. This will be repeated after three months of training and training intensity will be adjusted to maintain the training stimulus at the same relative intensity. The goal is for each volunteer to achieve an exercise intensity of 75-85% maintained for a continuous 30 minutes performed three times each week. A maximum FES-rowing test will be performed at the end of the six months of FES-RT to determine increases in fitness.

1. ARMS-ONLY-RT GROUP

Training sessions will be 3 times per week for 26 weeks. To parallel the FES-RT, the initial training sessions will also consist of 6 sets of arms-only rowing for five minutes at 60% of VO2peak with a work-to-rest ratio of 2:1 and progress over the six months to an exercise intensity of 75-85% maintained for 30 minutes performed three times each week. A maximum arms-only rowing test will be performed at baseline. This will be repeated after three months of training and training intensity will be adjusted to maintain the training stimulus at the same relative intensity. A maximum arms-only rowing test will be performed at the end of the six months of training to determine increases in fitness.

1. WAIT-LIST GROUP

The wait list group will not participate in any training for 6 months. A maximum arms-only rowing test will be performed immediately after enrollment, after initial familiarization with arms-only-RT equipment (usually 2-3 sessions) and will be repeated after 3 and 6 months

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Three intervention groups (Control, AO-Row, and FES-RT) run in parallelThree intervention groups (Control, AO-Row, and FES-RT) run in parallel
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Hybrid-FES Exercise to Prevent Cardiovascular Declines in Acute SCI
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Mar 1, 2020
• Actual Study Completion Date: Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FES-row-training Subjects will perform 6 months of FES-row-training.	Other: FES-row-training
Other: Wait-list time control Subjects perform 6 months of their standard of care	Other: Time Control
Active Comparator: Arms-only-row-training Subjects will perform 6 months of arms-only row training	Other: Arms-only-row training

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Exercise Capacity at 6 Months [Baseline and 6 months]

   Volunteers will perform an incremental exercise test of FES- or arms-only rowing to determine maximal oxygen uptake.

2. Change From Baseline in Visceral Adiposity at 6 Months [Baseline, 6 months]

   We will use a 5th generation General Electric Healthcare dual x-ray absorptiometry(DXA) scanner for regional fat measurements, the DXA software can be used to define standard regions that will allow comparability of measurements throughout the study.

3. Change From Baseline in Myocardial Structure at 6 Months. [Baseline and 6 months]

   Echocardiography was performed using a commercially available system(Vivid-1, General Electric Healthcare)to obtain measures of left ventricular wall thickness and left ventricular diastolic function.

4. Change From Baseline in Insulin Sensitivity at 6 Months. [Baseline and 6 months]

   Blood will be taken via standard venipuncture to measure the homeostasis model assessment of insulin resistance (HOMA-IR). HOMA-IR is a measure of insulin resistance/sensitivity calculated by multiplying fasting insulin (μU/mL) by fasting glucose (mg/dL) and divided by a constant (405). A higher value indicates higher insulin resistance.

5. Change From Baseline in Blood Lipids at 6 Months [Baseline and 6 months]

   Blood will be taken via standard venipuncture to measure: total cholesterol.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Spinal cord injured outpatients aged 18-40

• medically stable

• body mass index 18.5-30.0

• 3-12 months post SCI

• ASIA scale A, B or C at neurological level C5-T12

• able to follow directions

• leg muscles responsive to FES

Exclusion Criteria:

• hypertension

• significant arrhythmias

• coronary artery disease

• diabetes

• renal disease

• cancer

• epilepsy

• current use of cardioactive medications

• current grade 2 or greater pressure ulcers at relevant contact sites

• other neurological disease

• peripheral nerve compressions or rotator cuff tears that limit ability to row

• history of bleeding disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spaulding Hospital Cambridge	Cambridge	Massachusetts	United States	02138

Sponsors and Collaborators

• Spaulding Rehabilitation Hospital
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: J. Andrew Taylor, Ph.D., Spaulding Rehabilitation Hospital/Harvard Medical School

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 25, 2020

More Information

Publications

None provided.

• Responsible Party: J. Andrew Taylor, Director, Cardiovascular Research Laboratory, Spaulding Rehabilitation Hospital
• ClinicalTrials.gov Identifier: NCT02139436
• Other Study ID Numbers: 1R01HL117037; 1R01HL117037
• First Posted: May 15, 2014
• Last Update Posted: Mar 22, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Spinal Cord Injuries

Study Results

Participant Flow

Arm/Group Title	FES-row-training	Wait-list Time Control	Arms-only-row-training
Arm/Group Description	Subjects will perform 6 months of FES-row-training. FES-row-training	Subjects perform 6 months of their standard of care Time Control	Subjects will perform 6 months of arms-only row training Arms-only-row training
Period Title: Overall Study
STARTED	41	14	13
COMPLETED	41	14	13
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	FES-row-training	Wait-list Time Control	Arms-only-row-training	Total
Arm/Group Description	Subjects will perform 6 months of FES-row-training. FES-row-training	Subjects perform 6 months of their standard of care Time Control	Subjects will perform 6 months of arms-only row training Arms-only-row training	Total of all reporting groups
Overall Participants	41	14	13	68
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	41 100%	14 100%	13 100%	68 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28 (5)	28 (6)	28 (6)	28 (6)
Sex: Female, Male (Count of Participants)
Female	8 19.5%	1 7.1%	1 7.7%	10 14.7%
Male	33 80.5%	13 92.9%	12 92.3%	58 85.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 4.9%	1 7.1%	0 0%	3 4.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 7.3%	1 7.1%	3 23.1%	7 10.3%
White	28 68.3%	11 78.6%	8 61.5%	47 69.1%
More than one race	2 4.9%	1 7.1%	1 7.7%	4 5.9%
Unknown or Not Reported	6 14.6%	0 0%	1 7.7%	7 10.3%
Region of Enrollment (Count of Participants)
United States	41 100%	14 100%	13 100%	68 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Exercise Capacity at 6 Months
Description	Volunteers will perform an incremental exercise test of FES- or arms-only rowing to determine maximal oxygen uptake.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

The reported results represent a sub-population of the total number of subjects who completed the study. Some subjects did not complete the 6 month VO2 or their results were removed due to quality control or not meeting the criteria for a good test. Therefore, the presented numbers represent reliable and unbiased data.

Arm/Group Title	Waitlist Controls	Arms Only	FES-Rowing
Arm/Group Description	Controls (no structured exercise)	Arms Only Rowing	Functional Electrical Stimulation Rowing
Measure Participants	11	11	16
Baseline	14.6 (3.4)	18.5 (3.7)	17.1 (1.2)
6 Months	13.9 (2.5)	18.2 (4.4)	18.9 (1.5)

2. Primary Outcome

Title	Change From Baseline in Visceral Adiposity at 6 Months
Description	We will use a 5th generation General Electric Healthcare dual x-ray absorptiometry(DXA) scanner for regional fat measurements, the DXA software can be used to define standard regions that will allow comparability of measurements throughout the study.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

These are subgroups of the main study population. Exercise groups were combined.

Arm/Group Title	Waitlist	FES Rowing	Arms-Only Rowing
Arm/Group Description	Subjects continued with standard of care and did not perform and structured exercise	Subjects that performed FES-rowing	Subjects that only performed Arms-only rowing
Measure Participants	6	18	7
Baseline	13649 (1320)	10503 (1235)	10945 (2310)
6-Months	16057 (1952)	11247 (1390)	12197 (2492)

3. Primary Outcome

Title	Change From Baseline in Myocardial Structure at 6 Months.
Description	Echocardiography was performed using a commercially available system(Vivid-1, General Electric Healthcare)to obtain measures of left ventricular wall thickness and left ventricular diastolic function.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

The reported results represent a sub-population of the total number of subjects who completed the study. Some subjects did not complete the 6 month echocardiography or their results were removed due to quality control or not meeting the criteria for a good test. Therefore, the presented numbers represent reliable and unbiased data.

Arm/Group Title	Waitlist Controls	Arms Only	FES-Rowing
Arm/Group Description	Controls (no structured exercise)	Arms Only Rowing	Functional Electrical Stimulation Rowing
Measure Participants	7	6	17
Baseline	136 (4)	149 (5)	143 (2)
6 Months	129 (8)	133 (4)	138 (4)

4. Primary Outcome

Title	Change From Baseline in Insulin Sensitivity at 6 Months.
Description	Blood will be taken via standard venipuncture to measure the homeostasis model assessment of insulin resistance (HOMA-IR). HOMA-IR is a measure of insulin resistance/sensitivity calculated by multiplying fasting insulin (μU/mL) by fasting glucose (mg/dL) and divided by a constant (405). A higher value indicates higher insulin resistance.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

The reported results represent a sub-population of the total number of subjects who completed the study. Some subjects did not complete the 6 month blood draw. Therefore, the presented numbers represent reliable and unbiased data.

Arm/Group Title	Waitlist Controls	Arms Only	FES-Rowing
Arm/Group Description	Controls (no structured exercise)	Arms Only Rowing	Functional Electrical Stimulation Rowing
Measure Participants	4	2	16
Baseline	2.7 (1.7)	0.9 (0.1)	1.4 (0.5)
6 Months	3.1 (1.5)	0.6 (0.2)	1.7 (0.6)

5. Primary Outcome

Title	Change From Baseline in Blood Lipids at 6 Months
Description	Blood will be taken via standard venipuncture to measure: total cholesterol.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

The reported results represent a sub-population of the total number of subjects who completed the study. Some subjects did not complete the 6 month blood draw. Therefore, the presented numbers represent reliable and unbiased data.

Arm/Group Title	FES-row-training	Wait-list Time Control	Arms-only-row-training
Arm/Group Description	Subjects will perform 6 months of FES-row-training. FES-row-training	Subjects perform 6 months of their standard of care Time Control	Subjects will perform 6 months of arms-only row training Arms-only-row training
Measure Participants	16	4	2
Baseline	170 (8)	157 (9)	158 (4)
6 Months	171 (8)	141 (10)	149 (4)

Adverse Events

Time Frame	up to 6 months
Arm/Group Title	FES-row-training		Wait-list Time Control		Arms-only-row-training
Arm/Group Description	Subjects will perform 6 months of FES-row-training. FES-row-training		Subjects perform 6 months of their standard of care Time Control		Subjects will perform 6 months of arms-only row training Arms-only-row training
All Cause Mortality
	FES-row-training		Wait-list Time Control		Arms-only-row-training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/14 (0%)		0/13 (0%)
Serious Adverse Events
	FES-row-training		Wait-list Time Control		Arms-only-row-training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		1/14 (7.1%)		1/13 (7.7%)
Cardiac disorders
Autonomic Dysreflexia	0/41 (0%)	0	1/14 (7.1%)	2	1/13 (7.7%)	2
Other (Not Including Serious) Adverse Events
	FES-row-training		Wait-list Time Control		Arms-only-row-training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/41 (19.5%)		0/14 (0%)		1/13 (7.7%)
Cardiac disorders
Low Blood Pressure	1/41 (2.4%)	1	0/14 (0%)	0	0/13 (0%)	0
Elevated Blood Pressure	1/41 (2.4%)	1	0/14 (0%)	0	0/13 (0%)	0
Gastrointestinal disorders
Nausea	3/41 (7.3%)	3	0/14 (0%)	0	0/13 (0%)	0
Musculoskeletal and connective tissue disorders
Arthritis	2/41 (4.9%)	2	0/14 (0%)	0	0/13 (0%)	0
Skin and subcutaneous tissue disorders
Skin Ulcer	1/41 (2.4%)	1	0/14 (0%)	0	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.