Spinal Cord InjuryPhase 2/3NCT05008484
Effects of Electrical Stimulation and Vitamin D Supplementation on Bone Health Following Spinal Cord Injury.
A Phase 2/3 study testing NMES, Vitamin D and Passive movement in people with Spinal Cord Injury, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Neurogenic osteoporosis is a common complication of spinal cord injury (SCI) that is associated with low impact bone fractures. It is concerning that more than 46,000 Veterans affected with SCI and are at risk of osteoporosis and possible low impact fractures. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- NMES, Vitamin D and Passive movement
- Type of treatment
- Pill or oral medicine, Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2021to 13 Jun 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- To be included, participants will have to:
- Be 18-65 years of age
- Have history of traumatic SCI ( 1-year) with NLI of C8-T10 and AIS A or B (confirmed by AIS examination performed by PI or a qualified Provider
- Have a caregiver who is available and willing to be trained to apply intervention protocol in the home (placing weights and positioning the Veteran) throughout study duration
- Be a wheelchair user for primary mode of mobility
- Have Knee extensors that must respond to standard surface electrical stimulation procedures (stimulation frequency procedures, 30 Hz; pulse duration:1 ms and amplitude of the current of less than200 mA)
Show all 10Show fewer
- Be able to receive written clearance from their medical Providers to ensure safety of participants
- Be a Veteran (male or female), however, the Department of Veteran Affairs has limited number of female Veterans, especially those with motor complete injury at level C8-T10 (currently, there are only 3 female Veterans with the target NLI in our SCI registry). Hence, inclusion of women Veterans may be challenging due to this disparity in the SCI population. If we fail to recruit 20 Veterans, we may seek an IRB approval to recruit non-Veterans to meet our target sample size
- Have normal ECG
- Commit to undergo 9 months of trial; 4.5 months of open-kinematic chain resistance training followed by 4.5 months of closed-kinematic chain using simple rowing approach + Vit. D supplementation (Experimental group) or 9 months of passive movement +Vit D supplementation (control group)
Who cannot join
- Potential participants will be excluded if they exhibit any of the following:
- Neurological injury other than SCI
- Older than 65 years of age as they may likely have considerable amount of bone loss at that age
- Have severe osteoporosis because loading porous/fragile bone by electrical stimulation may result in bone fracture
- Those classified as AIS C \& D, as they may already be engaging in weight bearing activities that may confound the results of this trial
- Unhealed or unstable fractures in either lower or upper extremities
Show all 20Show fewer
- Severe scoliosis, deformities in the hip, knee, or ankles OR impaired range-of-motion, as these could be a barrier to safe positioning on the rowing machine, and on MRI or DXA tables
- No caregiver or family member/significant other, willing to help with placing weights and positioning participants' lower extremities on the rowing machine
- Untreated or uncontrolled hypertension (systolic blood pressure (BP) > 140 mmHg; diastolic BP > 90 mmHg), and/or sudden hypotension upon transferring from bed to wheelchair, characterized by a drop in BP by 20 mmHg (especially in persons with tetraplegia) or heart rate > 100 beats per minute
- Anti-coagulation or anti-platelet therapy (including aspirin)
- Implanted pacemakers, implanted defibrillator devices or any metallic implants including knee or hip implants
- Presence of bullets in vertebral column or shrapnel anywhere in the body that may interfere with MRI procedure
- Other medical conditions including cardiovascular disease, uncontrolled type II DM, active deep vein thrombosis (DVT), uncontrolled autonomic dysreflexia, use of insulin for DM management, pressures injuries of stage 3 or higher, or active urinary tract infection
- Severe hypercalcemia (serum calcium > 16mg/dl), stage III-V kidney disease, post-menopausal or estrogen dependent female, and men undergoing anti-androgen therapy or are post orchiectomy
- DXA total body T-score less than -2.5. Total hip BMD T-scores < -3.5 and knee BMD scores of less than 0.6 g/cm2
- Untreatable severe spasticity bearing on potential participants' activities of daily living, such as transfers from bed to wheelchair or maintaining position in wheelchair
- Any psychiatric illness confounding judgment or cognitive impairment in participant or caregiver who is expected to help participant in the trial
- Those with prosthetic lower limbs
- Any condition that, in the judgment of the PI or other medical Providers, preclude safe participation in the study and/or has the potential to expose/increase participant's risk of infection
- Unable to tolerate increasing either electrical stimulation current or weights to the lower legs for any reason
Trial locations and contacts
1 site in 1 country.
United States1 site
Hunter Holmes McGuire VA Medical Center, Richmond, VA
Richmond, Virginia, 23249-0001
About this study
Official title: Effects of Electrical Stimulation and Vitamin D Supplementation on Bone Health Following Spinal Cord Injury
Neurogenic osteoporosis is a common complication of spinal cord injury (SCI) that is associated with low impact bone fractures. It is concerning that more than 46,000 Veterans affected with SCI and are at risk of osteoporosis and possible low impact fractures. About fifty percent of all individuals with SCI will develop low impact fracture in their life time. The management of osteoporosis-related fractures can impose substantial economic burden on the health care system, the individual and the families. Previous studies did not succeed in reversing the process of bone loss after SCI. In the present pilot study, we will evaluate the effect of Neuromuscular Electrical Stimulation Resistance Training in combination with oral Vitamin D supplementation, on bone quality in Veterans with chronic SCI, using a randomized experimental design.
Read the detailed description
Neurogenic osteoporosis is a devastating problem that is likely to impact 46,000 Veterans with chronic spinal cord injury (SCI). It is typically associated with low impact fractures of long bones and other medical comorbidities. It is estimated that approximately fifty percent of all individuals with SCI will develop low impact fracture during their lifetime. The management of osteoporosis related fractures can impose substantial economic burden on the health care system, individuals with SCI and their families. Advancement in medical research clearly indicated that neurogenic osteoporosis is linked to reduced loading and Vitamin D (Vit D) deficiency. Our pilot work indicated that a simple rehabilitation paradigm targeting towards evoking skeletal muscle hypertrophy may attenuate deterioration in trabecular bone parameters after SCI. Evoked resistance training (RT) using surface neuromuscular electrical stimulation (NMES) has been shown as a successful and feasible home-based approach to load skeletal muscles after SCI. Our earlier results may imply long-term compliance and adherence if successfully applied in conjunction with a telehealth approach. In the present study, we propose a simple home-based approach of using NMES RT in conjunction with oral Vit D supplementation on trabecular bone quality in 20 Veterans with chronic SCI. Data will include measurements of trabecular bone quality as determined by magnetic resonance imaging (MRI) and bone biomarkers associated with the process of bone remodeling.
Twenty participants with chronic (> 1-year post-injury) motor complete (AIS A and B) SCI (18 to 65 years of age) will be randomly assigned into either NMES RT plus 2000IU of Vit D (10 participants) or passive movement plus 2000IU Vit D (10 participants) to participate in a repeated measure design trial for 9 months. The NMES RT plus Vit D will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach. This pilot work will have two main specific aims. Aim 1. To determine the impact of home-based NMES RT protocol plus oral Vit D supplementation compared to passive movement plus oral Vit D on bone microarchitectural properties. Aim 2. To determine the impact of home-based NMES RT protocol plus oral Vit D compared to passive movement and Vit D supplementation on biomarkers of bone formation and bone resorption.
- Conditions
- Spinal Cord Injury
- Being tested
- NMES, Vitamin D, Passive movement
- Keywords
- Vitamin D, Electrical Stimulation, Bone Density, Cancellous Bone, Spinal Cord Injury, Rehabilitation, Rowing Exercise
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMESDevice
Also called Intervention
Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach
Vitamin DDrug
Also called Concomitant therapy
2000IU oral vitamin D supplementation daily for 9 months
Passive movementBehavioural
Also called Control
Subjects will perform simple passive movement exercise for their legs while sitting in their wheelchairs at their home. The frequency of the training will be twice weekly
| Study group | Role | What they receive |
|---|---|---|
| NMES Plus Vitamin D | Experimental | Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach and 2000IU oral vitamin D supplementation daily for 9 months. Receives: Device: NMES; Drug: Vitamin D |
| Passive movement plus vitamin D | Active comparator | Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Receives: Drug: Vitamin D; Behavioral: Passive movement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months
The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae.
Measured: 4.5 months
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 9 Months
The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another set of 30 slices starting with the proximal end of the tibia. The metric used was the median change from baseline to 9 months. Higher values indicate improved Tb. PW.
Measured: 9 months
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 4.5 Months
The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate poorer bone health. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia.
Measured: 4.5 months
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 9 Months
The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 beginning with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae.
Measured: 9 months
Change in Trabecular Network Area Density (Tb.NA) Measured in mm^2/mm^3) at 4.5 Months
The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia.
Measured: 4.5 months
Change in Trabecular Network Area Density (Tb.NA) as Measured by MRI at 9 Months
The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia.
Measured: 9 months
Secondary outcomes (14)
Change in Bone Mineral Density in Distal Femur as Measured by Dual Energy X-ray Absorptiometry (DXA) Scan
A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L \& R) of the body (hip, knee), as well as the lumbar spine.
Measured: 4.5 months
Change in Distal Femur Bone Mineral Density
A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L \& R) of the body (hip, knee), as well as the lumbar spine.
Measured: 9 months
Change in Proximal Tibia Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) Scan
A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L \& R) of the body (hip, knee), as well as the lumbar spine.
Measured: 4.5 months
Change in Proximal Tibia Bone Mineral Density as Measured by a Dual-energy X-ray Absorptiometry (DXA) Scan
A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L \& R) of the body (hip, knee), as well as the lumbar spine.
Measured: 9 months
Change in Bone Formation Marker - Procollagen Type 1 N-terminal Propeptide (P1NP) in mcg/L
Fasting blood samples were collected by venipuncture by the same individual at roughly the same time of day and under similar conditions to evaluate P1NP, a marker of bone formation. Samples were analyzed at Quest Diagnostics (Nichols Institute, Chantilly, VA). The reference range for P1NP is 30-110 mcg/L, and an increase indicates poor bone health.
Measured: 4.5 months
Change in Bone Formation Marker - Procollagen Type 1 Intact N-Propeptide (P1NP) Measured in mcg/L
Fasting blood samples were collected by venipuncture by the same individual at roughly the same time of day and under similar conditions to evaluate P1NP, a marker of bone formation. Samples were analyzed at Quest Diagnostics (Nichols Institute, Chantilly, VA). The reference range for P1NP is 30-110 mcg/L, and an increase indicates poor bone health.
Measured: 9 months
Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)
CTX is a biochemical marker of bone resorption. Fasting blood samples were collected from participants via venipuncture by the same person at approximately the same time of day and under similar conditions to measure CTX (pg/mL). The samples were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). Sex and age-related reference ranges for males are: 18-29 years (87-1200), 30-39 years (70-780), 40-49 years (60-700), and 50-68 years (87-345). CTX is released into circulation when osteoclasts break down bone matrix; therefore, higher levels indicate increased osteoclastic activity and faster bone turnover.
Measured: 4.5 months
Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)
CTX is a biochemical marker of bone resorption. Fasting blood samples were collected from participants via venipuncture by the same person at approximately the same time of day and under similar conditions to measure CTX (pg/mL). The samples were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). Sex and age-related reference ranges for males are as follows: 18-29 years (87-1200), 30-39 years (70-780), 40-49 years (60-700), and 50-68 years (87-345). CTX is released into circulation when osteoclasts break down bone matrix; therefore, higher levels indicate increased osteoclastic activity and faster bone turnover.
Measured: 9 months
Change in Serum 25-hydroxyvitamin D [25(OD)D] Level
25-hydroxyvitamin D is the major circulating form of vitamin D and the most reliable biochemical indicator of an individual's vitamin D status.
It is essential for maintaining bone strength, balance of minerals, and overall bone integrity. Adequate levels of 25(OH)D enhance intestinal calcium absorption for normal bone formation and remodeling. When vitamin D levels are low, calcium absorption decreases, leading to secondary hyperparathyroidism, which in turn increases bone resorption and weakens bone structure. The normal range is 32 to 100 ng/mL. Less than 20ng/mL is considered a deficiency, and 20 to 29 ng/mL is insufficiency.
Measured: 4.5 months
Change in Serum 25-hydroxyvitamin D Level
25-hydroxyvitamin D is the main circulating form of vitamin D and the most reliable biochemical marker of an individual's vitamin D status. Vitamin D is crucial for maintaining bone strength, mineral balance, and overall bone health. Adequate levels of 25(OH)D improve intestinal calcium absorption, which is vital for normal bone formation and remodeling. When vitamin D levels are low, calcium absorption drops, leading to secondary hyperparathyroidism, which then increases bone resorption and weakens bone structure. The normal range is 32 to 100 ng/mL. Less than 20 ng/mL is considered a deficiency, and 20 to 29 ng/mL indicates insufficiency.
Measured: 9 months
Change in Quality-of-life Measure: Physical Health (Scored on 1-5 Likert Scale)
The secondary outcome measure was the WHO Quality of Life (WHOQOL)-BREF, a 26-item self-administered questionnaire developed by WHO to assess quality of life across four domains, including two general items. Each item is rated on a 5-point Likert scale (1 = negative or low perception, 5 = positive or high perception). The instrument includes four health domains: physical health, psychological health, social relationships, and environmental engagement. Physical health (7 items) evaluates energy, fatigue, sleep, mobility, pain, and activities of daily living. The maximum score for this domain is 100, and a higher score indicates a better quality of life.
Measured: 9 months
Change in Quality-of-life Measure- Psychological Health
The WHOQOL-BREF instrument was used to assess QOL in four domains of health, including: physical health, psychological health, social relationships, and environmental engagement. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Psychological health (6 items) measures self-esteem, body image, negative and positive feelings, and concentration. A higher score denotes higher psychological health.
Measured: 9 months
Change in Quality-of-life Measure- Social Relationships Domain
The WHOQOL-BREF instrument was used to assess QOL in four domains of health, including: physical health, psychological health, social relationships, and environment. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Social relationships (3 items) assess personal relationships, social support, and sexual life. A higher score denotes a higher social relationships.
Measured: 9 months
Change in Quality-of-life Measure-environmental Engagement Domain
The WHOQOL-BREF instrument was used to assess QOL in four domains of health participants, including: physical health, psychological health, social relationships, and environmental engagement. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Environmental engagement (8 items) assesses financial resources, safety, home environment, health care access, and opportunities for recreation and learning. A Higher score denotes better environmental engagement.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study start1 Oct 2021
- Primary completion13 Jun 2024
- Study completion13 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- There are two groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Virginia Commonwealth University, NYU Langone Health
- Responsible party
- Sponsor
- Investigators
- Dora E Ifon, PhD, Principal investigator, Hunter Holmes McGuire VA Medical Center, Richmond, VA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05008484
- Sponsor's protocol ID
- B3529-M
- Status last verified
- Jan 2026
- First submitted
- 6 Aug 2021
- Last updated
- 23 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Holman ME, Chang G, Ghatas MP, Saha PK, Zhang X, Khan MR, Sima AP, Adler RA, Gorgey AS. Bone and non-contractile soft tissue changes following open kinetic chain resistance training and testosterone treatment in spinal cord injury: an exploratory study. Osteoporos Int. 2021 Jul;32(7):1321-1332. doi: 10.1007/s00198-020-05778-2. Epub 2021 Jan 14.
PubMed 33443609Ifon DE, Ghatas MP, Davis JC, Khalil RE, Adler RA, Gorgey AS. Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury: A case matched report. World J Orthop. 2020 Oct 18;11(10):453-464. doi: 10.5312/wjo.v11.i10.453. eCollection 2020 Oct 18.
PubMed 33134108
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Electrical Stimulation and Vitamin D Supplementation on Bone Health Following Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT05008484
- Acronym / sponsor ID
- B3529-M
- Conditions
- Spinal Cord Injury
- Keywords
- Vitamin D, Electrical Stimulation, Bone Density, Cancellous Bone, Spinal Cord Injury, Rehabilitation, Rowing Exercise
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Virginia Commonwealth University, NYU Langone Health
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 13 Jun 2024 (actual)
- Study completion
- 13 Jun 2024 (actual)
- First posted
- 17 Aug 2021 (actual)
- Results
- Posted 23 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neurogenic osteoporosis is a common complication of spinal cord injury (SCI) that is associated with low impact bone fractures. It is concerning that more than 46,000 Veterans affected with SCI and are at risk of osteoporosis and possible low impact fractures. About fifty percent of all individuals with SCI will develop low impact fracture in their life time. The management of osteoporosis-related fractures can impose substantial economic burden on the health care system, the individual and the families. Previous studies did not succeed in reversing the process of bone loss after SCI. In the present pilot study, we will evaluate the effect of Neuromuscular Electrical Stimulation Resistance Training in combination with oral Vitamin D supplementation, on bone quality in Veterans with chronic SCI, using a randomized experimental design.
Detailed description
Neurogenic osteoporosis is a devastating problem that is likely to impact 46,000 Veterans with chronic spinal cord injury (SCI). It is typically associated with low impact fractures of long bones and other medical comorbidities. It is estimated that approximately fifty percent of all individuals with SCI will develop low impact fracture during their lifetime. The management of osteoporosis related fractures can impose substantial economic burden on the health care system, individuals with SCI and their families. Advancement in medical research clearly indicated that neurogenic osteoporosis is linked to reduced loading and Vitamin D (Vit D) deficiency. Our pilot work indicated that a simple rehabilitation paradigm targeting towards evoking skeletal muscle hypertrophy may attenuate deterioration in trabecular bone parameters after SCI. Evoked resistance training (RT) using surface neuromuscular electrical stimulation (NMES) has been shown as a successful and feasible home-based approach to load skeletal muscles after SCI. Our earlier results may imply long-term compliance and adherence if successfully applied in conjunction with a telehealth approach. In the present study, we propose a simple home-based approach of using NMES RT in conjunction with oral Vit D supplementation on trabecular bone quality in 20 Veterans with chronic SCI. Data will include measurements of trabecular bone quality as determined by magnetic resonance imaging (MRI) and bone biomarkers associated with the process of bone remodeling.
Twenty participants with chronic (> 1-year post-injury) motor complete (AIS A and B) SCI (18 to 65 years of age) will be randomly assigned into either NMES RT plus 2000IU of Vit D (10 participants) or passive movement plus 2000IU Vit D (10 participants) to participate in a repeated measure design trial for 9 months. The NMES RT plus Vit D will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach. This pilot work will have two main specific aims. Aim 1. To determine the impact of home-based NMES RT protocol plus oral Vit D supplementation compared to passive movement plus oral Vit D on bone microarchitectural properties. Aim 2. To determine the impact of home-based NMES RT protocol plus oral Vit D compared to passive movement and Vit D supplementation on biomarkers of bone formation and bone resorption.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- There are two groups
| Arm | Type | Receives |
|---|---|---|
| NMES Plus Vitamin D | Experimental | Device: NMES, Drug: Vitamin DSubjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach and 2000IU oral vitamin D supplementation daily for 9 months. |
| Passive movement plus vitamin D | Active comparator | Drug: Vitamin D, Behavioral: Passive movementSubjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Be 18-65 years of age
- Have history of traumatic SCI ( 1-year) with NLI of C8-T10 and AIS A or B (confirmed by AIS examination performed by PI or a qualified Provider
- Have a caregiver who is available and willing to be trained to apply intervention protocol in the home (placing weights and positioning the Veteran) throughout study duration
- Be a wheelchair user for primary mode of mobility
- Have Knee extensors that must respond to standard surface electrical stimulation procedures (stimulation frequency procedures, 30 Hz; pulse duration:1 ms and amplitude of the current of less than200 mA)
Key exclusion criteria (20 listed)
- Neurological injury other than SCI
- Older than 65 years of age as they may likely have considerable amount of bone loss at that age
- Have severe osteoporosis because loading porous/fragile bone by electrical stimulation may result in bone fracture
- Those classified as AIS C \& D, as they may already be engaging in weight bearing activities that may confound the results of this trial
- Unhealed or unstable fractures in either lower or upper extremities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NMESAlso: InterventionSubjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach | Device | NMES Plus Vitamin D |
| Vitamin DAlso: Concomitant therapy2000IU oral vitamin D supplementation daily for 9 months | Drug | NMES Plus Vitamin D, Passive movement plus vitamin D |
| Passive movementAlso: ControlSubjects will perform simple passive movement exercise for their legs while sitting in their wheelchairs at their home. The frequency of the training will be twice weekly | Behavioural | Passive movement plus vitamin D |
Primary outcome
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months
Time frame: 4.5 months
The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae.
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 9 Months
Time frame: 9 months
The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another set of 30 slices starting with the proximal end of the tibia. The metric used was the median change from baseline to 9 months. Higher values indicate improved Tb. PW.
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 4.5 Months
Time frame: 4.5 months
The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate poorer bone health. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia.
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 9 Months
Time frame: 9 months
The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 beginning with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae.
Change in Trabecular Network Area Density (Tb.NA) Measured in mm^2/mm^3) at 4.5 Months
Time frame: 4.5 months
The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia.
Change in Trabecular Network Area Density (Tb.NA) as Measured by MRI at 9 Months
Time frame: 9 months
The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia.
14 secondary outcomes
Change in Bone Mineral Density in Distal Femur as Measured by Dual Energy X-ray Absorptiometry (DXA) Scan
Time frame: 4.5 months
Change in Distal Femur Bone Mineral Density
Time frame: 9 months
Change in Proximal Tibia Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) Scan
Time frame: 4.5 months
Change in Proximal Tibia Bone Mineral Density as Measured by a Dual-energy X-ray Absorptiometry (DXA) Scan
Time frame: 9 months
Change in Bone Formation Marker - Procollagen Type 1 N-terminal Propeptide (P1NP) in mcg/L
Time frame: 4.5 months
Change in Bone Formation Marker - Procollagen Type 1 Intact N-Propeptide (P1NP) Measured in mcg/L
Time frame: 9 months
Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)
Time frame: 4.5 months
Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)
Time frame: 9 months
Change in Serum 25-hydroxyvitamin D [25(OD)D] Level
Time frame: 4.5 months
Change in Serum 25-hydroxyvitamin D Level
Time frame: 9 months
Change in Quality-of-life Measure: Physical Health (Scored on 1-5 Likert Scale)
Time frame: 9 months
Change in Quality-of-life Measure- Psychological Health
Time frame: 9 months
Change in Quality-of-life Measure- Social Relationships Domain
Time frame: 9 months
Change in Quality-of-life Measure-environmental Engagement Domain
Time frame: 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33443609Holman ME, Chang G, Ghatas MP, Saha PK, Zhang X, Khan MR, Sima AP, Adler RA, Gorgey AS. Bone and non-contractile soft tissue changes following open kinetic chain resistance training and testosterone treatment in spinal cord injury: an exploratory study. Osteoporos Int. 2021 Jul;32(7):1321-1332. doi: 10.1007/s00198-020-05778-2. Epub 2021 Jan 14.
- Background: PubMed 33134108Ifon DE, Ghatas MP, Davis JC, Khalil RE, Adler RA, Gorgey AS. Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury: A case matched report. World J Orthop. 2020 Oct 18;11(10):453-464. doi: 10.5312/wjo.v11.i10.453. eCollection 2020 Oct 18.
- Individual participant dataSharing planned: No
Related trials for Spinal Cord Injury
Recruiting
Evaluating Long-term Use of a Pediatric Robotic Exoskeleton (P.REX/Agilik) to Improve Gait in Children With Movement Disorders
Cerebral Palsy, Muscular Dystrophy
Active, not recruitingObservational study
Nerve Transfer Surgery to Restore Upper-limb Function After Cervical Spinal Cord Injury
Spinal Cord Injury, Spinal Cord Injury at C5-C7 Level
Recruiting
Implementing a Decision Support Tool to Prevent Community-Acquired Pressure Injury in Spinal Cord Injury (SCI) in the Spinal Cord Injury Clinic
Spinal Cord Injury, Pressure Injury
Recruiting
Feasibility of the BrainGate2 Neural Interface System in Persons With Tetraplegia (BG-Tablet-01)
Brainstem Stroke, ALS
Recruiting
A Neuroprosthesis for Seated Posture and Balance
Spinal Cord Injury, Paralysis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dora E Ifon, PhD principal investigator
Hunter Holmes McGuire VA Medical Center, Richmond, VA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing NMES, Vitamin D and Passive movement in people with Spinal Cord Injury, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months (time frame: 4.5 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05008484, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.