Effects of Electrical Stimulation and Vitamin D Supplementation on Bone Health Following Spinal Cord Injury.

NCT05008484 | Completed Phase 2 Results FDA Drug FDA Device

• 1 other identifier: B3529-M
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Spinal Cord Injury

Keywords

Vitamin D; Electrical Stimulation; Bone Density; Cancellous Bone; Spinal Cord Injury; Rehabilitation; Rowing Exercise

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  9 months

Secondary Outcomes (14)

• Change in Bone Mineral Density in Distal Femur as Measured by Dual Energy X-ray Absorptiometry (DXA) Scan

  4.5 months

• Change in Distal Femur Bone Mineral Density

  9 months

• Change in Proximal Tibia Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) Scan

  4.5 months

• Change in Proximal Tibia Bone Mineral Density as Measured by a Dual-energy X-ray Absorptiometry (DXA) Scan

  9 months

• Change in Bone Formation Marker - Procollagen Type 1 N-terminal Propeptide (P1NP) in mcg/L

  4.5 months

Study Arms (2)

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.

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.

Drug: Vitamin D; Behavioral: Passive movement

Interventions

NMES DEVICE

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

Also known as: Intervention

NMES Plus Vitamin D

Vitamin D DRUG

2000IU oral vitamin D supplementation daily for 9 months

Also known as: Concomitant therapy

NMES Plus Vitamin D; Passive movement plus vitamin D

Passive movement BEHAVIORAL

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

Also known as: Control

Passive movement plus vitamin D

Eligibility Criteria

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

You may qualify if:

• 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)
• Be able to receive written clearance from their medical Providers to ensure safety of participants
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Virginia Commonwealth University: collaborator
• NYU Langone Health: collaborator

Study Sites (1)

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, 23249-0001, United States

Location

Related Publications (2)

• 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.

  PMID: 33443609 BACKGROUND

• Ifon 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.

  PMID: 33134108 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Methods; Vitamin D; Range of Motion, Articular

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Investigative Techniques; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Limitations and Caveats

The small sample size, only male participants, and a wide variation in participants' level of injury (C8-T10) and age, limit generalizability of the study findings to a broader spinal cord injury population.

Results Point of Contact

• Title: Dora E. Ifon
• Organization: McGuire VA Hospital

dora.ifon@va.gov

804-675-5455

Study Officials

• Dora E Ifon, PhD

  Hunter Holmes McGuire VA Medical Center, Richmond, VA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: There are two groups

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 17, 2021
• Study Start: October 1, 2021
• Primary Completion: June 13, 2024
• Study Completion: June 13, 2024
• Last Updated: January 23, 2026
• Results First Posted: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)