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临床试验/NCT05008484
NCT05008484
已完成
2 期

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

VA Office of Research and Development1 个研究点 分布在 1 个国家目标入组 6 人2021年10月1日

概览

阶段
2 期
干预措施
NMES
疾病 / 适应症
Spinal Cord Injury
发起方
VA Office of Research and Development
入组人数
6
试验地点
1
主要终点
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months
状态
已完成
最后更新
3个月前

概览

简要总结

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.

详细描述

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.

注册库
clinicaltrials.gov
开始日期
2021年10月1日
结束日期
2024年6月13日
最后更新
3个月前
研究类型
Interventional
研究设计
Parallel
性别
All

研究者

责任方
Sponsor

入排标准

入选标准

  • 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)

排除标准

  • 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)

研究组 & 干预措施

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.

干预措施: NMES

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.

干预措施: Vitamin D

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.

干预措施: Vitamin D

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.

干预措施: Passive movement

结局指标

主要结局

Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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.

次要结局

  • 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)
  • Change in Bone Formation Marker - Procollagen Type 1 Intact N-Propeptide (P1NP) Measured in mcg/L(9 months)
  • Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)(4.5 months)
  • Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)(9 months)
  • Change in Serum 25-hydroxyvitamin D [25(OD)D] Level(4.5 months)
  • Change in Serum 25-hydroxyvitamin D Level(9 months)
  • Change in Quality-of-life Measure: Physical Health (Scored on 1-5 Likert Scale)(9 months)
  • Change in Quality-of-life Measure- Psychological Health(9 months)
  • Change in Quality-of-life Measure- Social Relationships Domain(9 months)
  • Change in Quality-of-life Measure-environmental Engagement Domain(9 months)

研究点 (1)

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