Skeletal Muscle Hypertrophy and Cardio-Metabolic Benefits After Spinal Cord Injury
| Status: | Recruiting |
|---|---|
| Conditions: | Hospital, Orthopedic |
| Therapuetic Areas: | Orthopedics / Podiatry, Other |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 2/10/2019 |
| Start Date: | October 2015 |
| End Date: | September 2020 |
Spinal cord injury (SCI) is a devastating medical problem that affects thousands of civilian
and military personnel in the United States. Spinal cord injuries (SCI) predispose
individuals to impaired fitness, obesity, glucose intolerance and insulin resistance, placing
them at greater risk for diabetes and coronary artery disease. These are devastating problems
that occur frequently because of changes in body composition and reduced level of physical
activity. Skeletal muscle wasting plays a central role in altered metabolism after SCI.
Functional electrical stimulation (FES) is an effective rehabilitation tool that has been
used to train the paralyzed skeletal muscles and which has shown some ability to ameliorate
the deleterious effects of SCI on metabolism, particularly on insulin sensitivity. However,
its ability to reverse skeletal muscle wasting is modest; most studies report limited gains
in muscle mass and workload with highly variables outcomes from one study to another. This
proposal was stimulated by the findings that a program of neuromuscular electrical
stimulation resistance exercise prior to initiating functional electrical stimulation lower
extremity cycling (FES-LEC) improves the gains in muscle mass and workload observed with FES.
The specific objectives for the current proposal are to compare the impact of FES following
evoking skeletal muscle hypertrophy of the lower extremity versus initiating FES cycling
without introducing the hypertrophy effects on insulin sensitivity, control of blood sugar
levels, oxygen uptake and amounts of muscle tissue and fat deposition. These studies could
potentially have significant effects on thousands of people that will experience an SCI in
the future as well as those living with SCI where prolonged paralysis is a major quality of
life issue.
There is a major need to investigate the mechanisms lead to maximize the benefits of FES
applications and to understand cellular or molecular events that are associated with muscle
hypertrophy and lead to promoting metabolic health after SCI. The designed study will provide
a greater understanding regarding utilization of energy sources (like fats and sugars) in
muscle
and military personnel in the United States. Spinal cord injuries (SCI) predispose
individuals to impaired fitness, obesity, glucose intolerance and insulin resistance, placing
them at greater risk for diabetes and coronary artery disease. These are devastating problems
that occur frequently because of changes in body composition and reduced level of physical
activity. Skeletal muscle wasting plays a central role in altered metabolism after SCI.
Functional electrical stimulation (FES) is an effective rehabilitation tool that has been
used to train the paralyzed skeletal muscles and which has shown some ability to ameliorate
the deleterious effects of SCI on metabolism, particularly on insulin sensitivity. However,
its ability to reverse skeletal muscle wasting is modest; most studies report limited gains
in muscle mass and workload with highly variables outcomes from one study to another. This
proposal was stimulated by the findings that a program of neuromuscular electrical
stimulation resistance exercise prior to initiating functional electrical stimulation lower
extremity cycling (FES-LEC) improves the gains in muscle mass and workload observed with FES.
The specific objectives for the current proposal are to compare the impact of FES following
evoking skeletal muscle hypertrophy of the lower extremity versus initiating FES cycling
without introducing the hypertrophy effects on insulin sensitivity, control of blood sugar
levels, oxygen uptake and amounts of muscle tissue and fat deposition. These studies could
potentially have significant effects on thousands of people that will experience an SCI in
the future as well as those living with SCI where prolonged paralysis is a major quality of
life issue.
There is a major need to investigate the mechanisms lead to maximize the benefits of FES
applications and to understand cellular or molecular events that are associated with muscle
hypertrophy and lead to promoting metabolic health after SCI. The designed study will provide
a greater understanding regarding utilization of energy sources (like fats and sugars) in
muscle
Primary Objectives Aim #1: To determine the impact of 12+12 weeks of neuromuscular electrical
stimulation (NMES)+FES-LEC on oxygen uptake, insulin sensitivity and glucose uptake in adults
with SCI compared to control + FES-LEC.
Aim #2: To determine the impact of 12+12 weeks of NMES+FES-LEC on skeletal muscle size,
infiltration of intramuscular fat, visceral adiposity as well as fatigue resistance compared
to control+ FES-LEC.
. Aim #3 : To determine the impact of 12+12 weeks of NMES+FES-LEC on determinants of energy
metabolism, protein molecules involved in insulin signaling, muscle hypertrophy and oxygen
uptake (IRS-1, adenosine monophosphate kinase (AMPK), glucose transporter (GLUT-4), insulin
like growth factor (IGF-1), Akt, mammalian target of rapamycin (mTOR) and Peroxisome
proliferator-activated receptor coactivator (PGC-1 alpha) and electron transport chain
proteins compared to control + FES-LEC only.
Subjects: Forty eight chronic (1 year or more post-injury) individuals with motor complete
SCI will be recruited from the Hunter Holmes McGuire VA Spinal Cord Dysfunction registry and
Virginia Commonwealth University over 4 years.
Inclusion Criteria
1. All participants will be between 18-65 years old, men/women,
2. greater than one year post SCI,
3. Body mass index (BMI) < 30 Kg/m2.
4. Participants must have C5-L2 level of injury, traumatic motor complete or incomplete SCI
[American Spinal Injury Impairment Scale Classification (AIS A, B or C)].
Exclusion Criteria:
1. Participants with any of the following pre-existing medical conditions will be excluded
(cardiovascular disease, uncontrolled type II diabetes mellitus, uncontrolled
hypertension, and those on insulin, pressures sores stage 3 or greater), hematocrit
above 50% or urinary tract infection or symptoms.
2. Participants with osteoporosis (T-score equal or worse than -2.5 according to the World
Health recommendation) will be excluded.
3. Pregnant women and women who will be involved and become pregnant during the course of
the study will be excluded as well.
Study arms
1. NMES+FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice weekly
of 12 weeks of surface NMES and ankle weights followed by 12 additional weeks of twice
weekly of progressive FES-LEC using the RT300 bike. The total participation duration is
24 weeks +3 weeks for measurements.
2. Control + FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice
weekly of 12 weeks of passive leg extension/flexion with no ankle weights followed by 12
additional weeks of twice weekly of progressive FES-LEC using the RT300 bike. The total
participation duration is 24 weeks+3 weeks for measurements.
stimulation (NMES)+FES-LEC on oxygen uptake, insulin sensitivity and glucose uptake in adults
with SCI compared to control + FES-LEC.
Aim #2: To determine the impact of 12+12 weeks of NMES+FES-LEC on skeletal muscle size,
infiltration of intramuscular fat, visceral adiposity as well as fatigue resistance compared
to control+ FES-LEC.
. Aim #3 : To determine the impact of 12+12 weeks of NMES+FES-LEC on determinants of energy
metabolism, protein molecules involved in insulin signaling, muscle hypertrophy and oxygen
uptake (IRS-1, adenosine monophosphate kinase (AMPK), glucose transporter (GLUT-4), insulin
like growth factor (IGF-1), Akt, mammalian target of rapamycin (mTOR) and Peroxisome
proliferator-activated receptor coactivator (PGC-1 alpha) and electron transport chain
proteins compared to control + FES-LEC only.
Subjects: Forty eight chronic (1 year or more post-injury) individuals with motor complete
SCI will be recruited from the Hunter Holmes McGuire VA Spinal Cord Dysfunction registry and
Virginia Commonwealth University over 4 years.
Inclusion Criteria
1. All participants will be between 18-65 years old, men/women,
2. greater than one year post SCI,
3. Body mass index (BMI) < 30 Kg/m2.
4. Participants must have C5-L2 level of injury, traumatic motor complete or incomplete SCI
[American Spinal Injury Impairment Scale Classification (AIS A, B or C)].
Exclusion Criteria:
1. Participants with any of the following pre-existing medical conditions will be excluded
(cardiovascular disease, uncontrolled type II diabetes mellitus, uncontrolled
hypertension, and those on insulin, pressures sores stage 3 or greater), hematocrit
above 50% or urinary tract infection or symptoms.
2. Participants with osteoporosis (T-score equal or worse than -2.5 according to the World
Health recommendation) will be excluded.
3. Pregnant women and women who will be involved and become pregnant during the course of
the study will be excluded as well.
Study arms
1. NMES+FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice weekly
of 12 weeks of surface NMES and ankle weights followed by 12 additional weeks of twice
weekly of progressive FES-LEC using the RT300 bike. The total participation duration is
24 weeks +3 weeks for measurements.
2. Control + FES group (n =24; 2 days/week for 24 weeks); this group will undergo twice
weekly of 12 weeks of passive leg extension/flexion with no ankle weights followed by 12
additional weeks of twice weekly of progressive FES-LEC using the RT300 bike. The total
participation duration is 24 weeks+3 weeks for measurements.
Inclusion Criteria:
- All participants will be between 18-65 years old,
- men/women,
- Greater than one year post SCI,
- with body mass index (BMI) < 30 Kg/m2. .
- Participants must have traumatic motor complete or incomplete SCI C5-L2 level of
injury, American Spinal Injury Impairment Scale Classification (AIS A, B or C).
Exclusion Criteria:
- Participants with any of the following pre-existing medical conditions will be
excluded (cardiovascular disease, uncontrolled type II DM, uncontrolled hypertension,
and those on insulin, pressures sores stage 3 or greater), hematocrit above 50% or
urinary tract infection or symptoms.
- Participants with osteoporosis (T-score equal or worse than -2.5 according to the
World Health recommendation) will be excluded.
- Pregnant women and women who will be involved and become pregnant during the course of
the study will be excluded as well.
We found this trial at
3
sites
711 West Main Street
Richmond, Virginia 23220
Richmond, Virginia 23220
Principal Investigator: William Carter, MD
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Richmond, Virginia 23249
Principal Investigator: Ashraf S Gorgey, MPT, PhD, FACSM
Phone: 804-675-5000
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