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

Spinal Cord Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05008484
• Other study ID #: B3529-M
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 1, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

• 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)

Exclusion Criteria:

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

• 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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury
• Wounds and Injuries

Intervention

Device:
• NMES
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

Drug:
• Vitamin D
2000IU oral vitamin D supplementation daily for 9 months

Procedure:
• Passive movement
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. .

Locations

Country	Name	City	State
United States	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
VA Office of Research and Development	NYU Langone Health, Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Trabecular microarchitecture	Magnetic resonance imaging will be used in persons with SCI to measure trabecular bone parameters.	0. 4.5 months and 9 months
Primary	Changes in trabecular microarchitecture	Magnetic Resonance Imaging (MRI) was used to measure trabecular bone parameters in persons with chronic spinal cord injury.	0, 4.5 months and 9 months
Secondary	Changes in Bone mineral density	Dual energy x-ray absorptiometry will be used to measure knee bone mineral density in persons with SCI	0. 4.5 months and 9 months
Secondary	Changes in Muscle area	Magnetic resonance imaging will be used in persons with SCI to measure muscle cross-sectional area.	0. 4.5 months and 9 months
Secondary	Changes in Bone biomarkers	Blood samples from persons with SCI will be used to measure bone biomarkers.	0. 4.5 months and 9 months
Secondary	Changes in Quality of life (QOL)	WHO-QOL survey instrument will be used to measure QOL in persons with SCI. The scale is composed of 5 items that ranged from very poor or dissatisfied to very good or very satisfied.	0 and 9 months
Secondary	Changes in Bone biomarkers	Blood samples from persons with SCI will be used to measure bone biomarkers.	Blood samples from persons with SCI will be used to measure bone biomarkers.