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

• ClinicalTrials.gov Identifier: NCT05008484
• Recruitment Status: Recruiting
• First Posted: August 17, 2021
• Last Update Posted: August 29, 2022
• Sponsor: VA Office of Research and Development
• Collaborators: Virginia Commonwealth University; NYU Langone Health
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injury	Device: NMES; Drug: Vitamin D; Procedure: Passive movement	Phase 2; Phase 3

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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: There are two groups
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Electrical Stimulation and Vitamin D Supplementation on Bone Health Following Spinal Cord Injury.
• Actual Study Start Date: October 1, 2021
• Estimated Primary Completion Date: September 30, 2023
• Estimated Study Completion Date: September 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: NMES Plus Vitamin D; 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; 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
Experimental: Passive movement plus vitamin D; 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; 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. .

Outcome Measures

Primary Outcome Measures :

1. Changes in Trabecular microarchitecture [ Time Frame: 0. 4.5 months and 9 months ]
   Magnetic resonance imaging will be used in persons with SCI to measure trabecular bone parameters.

Secondary Outcome Measures :

1. Changes in Bone mineral density [ Time Frame: 0. 4.5 months and 9 months ]
   Dual energy x-ray absorptiometry will be used to measure knee bone mineral density in persons with SCI
2. Changes in Muscle area [ Time Frame: 0. 4.5 months and 9 months ]
   Magnetic resonance imaging will be used in persons with SCI to measure muscle cross-sectional area.
3. Changes in Bone biomarkers [ Time Frame: 0. 4.5 months and 9 months ]
   Blood samples from persons with SCI will be used to measure bone biomarkers.
4. Changes in Quality of life (QOL) [ Time Frame: 0 and 9 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Dora E Ifon, PhD; (804) 547-4723; Dora.Ifon@va.gov

Contact: Ashraf Gorgey, PhD PT; (804) 675-5000 ext 3386; ashraf.gorgey@va.gov

Locations

United States, Virginia

Hunter Holmes McGuire VA Medical Center, Richmond, VA; Recruiting

Richmond, Virginia, United States, 23249

Contact: Dora E Ifon, PhD 804-547-4723 Dora.Ifon@va.gov

Contact: Ashraf Gorgey, PhD PT (804) 675-5000 ext 3386 ashraf.gorgey@va.gov

Principal Investigator: Dora E Ifon, PhD

Sponsors and Collaborators

VA Office of Research and Development

Virginia Commonwealth University

NYU Langone Health

Investigators

• Principal Investigator: Dora E Ifon, PhD; Hunter Holmes McGuire VA Medical Center, Richmond, VA

More Information

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.

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.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT05008484
• Other Study ID Numbers: B3529-M
• First Posted: August 17, 2021
• Last Update Posted: August 29, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by VA Office of Research and Development:

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

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Vitamin D; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents