Trial Outcomes & Findings for Effects of Electrical Stimulation and Vitamin D Supplementation on Bone Health Following Spinal Cord Injury. (NCT NCT05008484)

Last Updated: 2026-01-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

6 participants

Primary outcome timeframe

4.5 months

Results posted on

2026-01-23

Participant Flow

Participants were recruited from a spinal cord injury outpatient clinic. One participant was referred by another participant.

One participant was excluded prior to the start of the study because he failed to complete baseline screening and did not respond to phone calls.

Participant milestones

Participant milestones
Measure	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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	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. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Overall Study STARTED	4	2
Overall Study COMPLETED	3	1
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	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. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=270 Participants	2 Participants n=4 Participants	6 Participants n=9 Participants
Age, Categorical >=65 years	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Age, Continuous	53.5 years n=270 Participants	42 years n=4 Participants	53 years n=9 Participants
Sex: Female, Male Female	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Sex: Female, Male Male	4 Participants n=270 Participants	2 Participants n=4 Participants	6 Participants n=9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Asian	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Black or African American	3 Participants n=270 Participants	1 Participants n=4 Participants	4 Participants n=9 Participants
Race (NIH/OMB) White	1 Participants n=270 Participants	1 Participants n=4 Participants	2 Participants n=9 Participants
Race (NIH/OMB) More than one race	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Baseline Trabecular plate width (Tb.PW) in μm as measured by MRI Tb.PW for left femur and tibia	1791.44 μm n=270 Participants	1779.66 μm n=4 Participants	1791.44 μm n=9 Participants
Baseline Trabecular plate width (Tb.PW) in μm as measured by MRI Tb.PW for right femur and tibia	1769.03 μm n=270 Participants	1829.0 μm n=4 Participants	1789.23 μm n=9 Participants
Baseline Trabecular spacing (Tb.Sp) (um) as measured by MRI Tb.Sp for left femur and tibia	576.16 μm n=270 Participants	430.68 μm n=4 Participants	486.66 μm n=9 Participants
Baseline Trabecular spacing (Tb.Sp) (um) as measured by MRI Tb.Sp for right femur and tibia	613.71 μm n=270 Participants	445.60 μm n=4 Participants	509.55 μm n=9 Participants
Baseline Trabecular network area density (Tb.NA) (mm^2/mm^3) measured by MRI Tb.NA for left femur and tibia	0.44 mm^2/mm^3 n=270 Participants	0.61 mm^2/mm^3 n=4 Participants	0.51 mm^2/mm^3 n=9 Participants
Baseline Trabecular network area density (Tb.NA) (mm^2/mm^3) measured by MRI Tb.NA for right femur and tibia	0.42 mm^2/mm^3 n=270 Participants	445.60 mm^2/mm^3 n=4 Participants	0.51 mm^2/mm^3 n=9 Participants
Baseline Distal Femur Bone Mineral Density (BMD) in g/cm2 as measured by DXA Left distal femur BMD	0.96 g/cm2 n=270 Participants	1.20 g/cm2 n=4 Participants	1.12 g/cm2 n=9 Participants
Baseline Distal Femur Bone Mineral Density (BMD) in g/cm2 as measured by DXA Right distal femur BMD	0.96 g/cm2 n=270 Participants	1.22 g/cm2 n=4 Participants	1.10 g/cm2 n=9 Participants
Baseline Proximal tibia Bone Mineral Density in g/cm2 as measured by DXA. Left proximal tibia BMD	0.97 g/cm2 n=270 Participants	1.50 g/cm2 n=4 Participants	1.19 g/cm2 n=9 Participants
Baseline Proximal tibia Bone Mineral Density in g/cm2 as measured by DXA. Right proximal tibia BMD	1.0 g/cm2 n=270 Participants	1.5 g/cm2 n=4 Participants	1.20 g/cm2 n=9 Participants
Baseline Bone formation marker (Procollagen Type 1 Intact N-Propeptide [P1NP] in mcg/L	39 mcg/L n=270 Participants	63.5 mcg/L n=4 Participants	46 mcg/L n=9 Participants
Baseline Bone resorption marker (C-telopeptide of Type I collagen [CTX]), in pg/mL	351.5 pg/mL n=270 Participants	531 pg/mL n=4 Participants	418 pg/mL n=9 Participants
Baseline Serum concentration of 25-hydroxyvitamin D in ng/mL	23.4 ng/mL n=270 Participants	26.05 ng/mL n=4 Participants	25.3 ng/mL n=9 Participants
Baseline Physical domain of Quality of life measure	72 units on a scale (0-100) n=270 Participants	75 units on a scale (0-100) n=4 Participants	72 units on a scale (0-100) n=9 Participants
Baseline Psychological health domain of Quality of life measure	65.5 units on a scale (0-100) n=270 Participants	81 units on a scale (0-100) n=4 Participants	81 units on a scale (0-100) n=9 Participants
Baseline Social relationship domain of Quality of life measure.	75 units on a scale (0-100) n=270 Participants	78 units on a scale (0-100) n=4 Participants	78 units on a scale (0-100) n=9 Participants
Baseline environmental engagement domain of Quality of life measure.	84.5 units on a scale (0-100) n=270 Participants	81 units on a scale (0-100) n=4 Participants	81 units on a scale (0-100) n=9 Participants

PRIMARY outcome

Timeframe: 4.5 months

Population: Participants (n = 6) with chronic motor-complete spinal cord injury (C8-T10) with ASIA impairment classification of A or B, completed an MRI at baseline and 4.5 months.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months Left Femur and TibiaTb.PW at 4.5 months	1785.42 μm Interval 1753.76 to 1809.26	1819.41 μm IQR values could not be calculated due to only 2 participants assessed within this Arm.
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months Right Femur and Tibia Tb.PW at 4.5 months	1805.52 μm Interval 1773.62 to 1816.2	1834.67 μm IQR values could not be calculated due to only 2 participants assessed within this Arm.

PRIMARY outcome

Timeframe: 9 months

Population: Four participants with chronic motor-complete spinal cord injury (C8-T10) and an ASIA impairment classification of A or B completed MRI at 9 months (n = 3 in the NMES + Vit. D group and n = 1 in the Passive movement + Vit. D group).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 9 Months Left Femur and Tibia Tb.PW at 9 months	1767.38 um Interval 1762.7 to 1779.56	1750.77 um IQR values could not be calculated due to only 1 participant assessed within this Arm.
Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 9 Months Right Femur and Tibia Tb.PW at 9 months	1786.44 um Interval 1775.62 to 1796.93	1734.01 um IQR values could not be calculated due to only 1 participant assessed within this Arm.

PRIMARY outcome

Timeframe: 4.5 months

Population: Six participants with chronic motor-complete spinal cord injury (C8-T10) and ASIA impairment classification of A or B completed MRI at 4.5 months (n = 4 in the NMES + Vit. D group and n = 2 in the Passive movement + Vit. D group).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 4.5 Months Right femur and tibia Tb.Sp at 4.5 months	556.84 um Interval 532.04 to 588.58	440.57 um IQR values could not be calculated due to only 1 participant assessed within this Arm.
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 4.5 Months Left femur and tibia Tb.Sp at 4.5 months	550.41 um Interval 523.63 to 583.66	463.22 um IQR values could not be calculated due to only 1 participant assessed within this Arm.

PRIMARY outcome

Timeframe: 9 months

Population: Four participants with motor complete spinal cord injury (C8-T10) ( 3 in the NMES + vit DArm and 1 in the Passive movement + Vit.D Arm) underwent MRI 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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 9 Months Left femur and tibia Tb.Sp at 9 months	494.33 um Interval 493.58 to 503.24	526.39 um IQR values could not be calculated due to only 1 participant assessed within this Arm.
Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 9 Months Right femur and tibia Tb.Sp at 9 months	484.05 um Interval 482.67 to 518.45	565.33 um IQR values could not be calculated due to only 1 participant assessed within this Arm,

PRIMARY outcome

Timeframe: 4.5 months

Population: All participants (n = 6) with chronic motor-complete spinal cord injury (C8-T10) and ASIA impairment classification of A or B completed an MRI at baseline and at 4.5 months. By 9 months, only four participants (n = 3 in the NMES + Vit. D group and n = 1 in the Passive movement + Vit. D group) completed the MRI after two participants (one in each group) voluntarily withdrew.

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Trabecular Network Area Density (Tb.NA) Measured in mm^2/mm^3) at 4.5 Months Right femur and tibiaTb.NA at 4.5 months	0.45 mm^2/mm^3 Interval 0.44 to 0.48	0.46 mm^2/mm^3 IQR values could not be calculated due to only 2 participants assessed within this Arm.
Change in Trabecular Network Area Density (Tb.NA) Measured in mm^2/mm^3) at 4.5 Months Left femur and tibia Tb.NA at 4.5 months	0.48 mm^2/mm^3 Interval 0.44 to 0.54	0.59 mm^2/mm^3 IQR values could not be calculated due to only 2 participants assessed within this Arm.

PRIMARY outcome

Timeframe: 9 months

Population: Four participants with motor complete spinal cord injury (C8-T10), underwent MRI of both knees upon completion of the trial.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Trabecular Network Area Density (Tb.NA) as Measured by MRI at 9 Months Left femur and tibia Tb.NA at 9 months	0.52 mm^2/mm^3 Interval 0.52 to 0.54	0.48 mm^2/mm^3 IQR values could not be calculated due to only 1 participant assessed within this Arm.
Change in Trabecular Network Area Density (Tb.NA) as Measured by MRI at 9 Months Right femur and tibia Tb.NA at 9 months	0.54 mm^2/mm^3 Interval 0.53 to 0.55	0.44 mm^2/mm^3 IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 4.5 months

Population: Six males with motor complete spinal cord injury (C8-T10) underwent DXA scans after 4.5 months in the trial.

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Bone Mineral Density in Distal Femur as Measured by Dual Energy X-ray Absorptiometry (DXA) Scan Left distal femur BMD	0.94 g/cm2 Interval 0.85 to 1.08	1.17 g/cm2 IQR values could not be calculated due to only 2 participants assessed within this study Arm.
Change in Bone Mineral Density in Distal Femur as Measured by Dual Energy X-ray Absorptiometry (DXA) Scan Right distal femur BMD	0.90 g/cm2 Interval 0.81 to 1.04	1.21 g/cm2 IQR values could not be calculated due to only 2 participants assessed within this study Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Four males with motor complete spinal cord injury (C8-T10) underwent DXA scans upon completing the trial.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Distal Femur Bone Mineral Density Left distal femur BMD	0.84 g/cm2 Interval 0.81 to 1.0	1.07 g/cm2 IQR values could not be calculated due to only 1 participant assessed within this Arm.
Change in Distal Femur Bone Mineral Density Right distal femur BMD	0.84 g/cm2 Interval 0.78 to 0.96	1.02 g/cm2 IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 4.5 months

Population: Four males with motor complete spinal cord injury (C1-T10) underwent DXA of the knees after 4.5 months of the trial.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Proximal Tibia Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) Scan Left proximal tibia BMD	0.97 gm/cm2 Interval 0.92 to 1.06	1.47 gm/cm2 IQR values could not be calculated due to only 2 participants assessed within this Arm.
Change in Proximal Tibia Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) Scan Right proximal tibia BMD	1.09 gm/cm2 Interval 0.93 to 1.24	1.42 gm/cm2 IQR values could not be calculated due to only 2 participants assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Four males with motor complete spinal cord injury (C8-T10) underwent DXA scan of the knees after 9 months of the trial.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Proximal Tibia Bone Mineral Density as Measured by a Dual-energy X-ray Absorptiometry (DXA) Scan Left proximal tibia BMD	1.02 gm/cm2 Interval 0.98 to 1.03	1.3 gm/cm2 IQR values could not be calculated due to only 1 participant assessed within this Arm.
Change in Proximal Tibia Bone Mineral Density as Measured by a Dual-energy X-ray Absorptiometry (DXA) Scan Right proximal tibia BMD	1.09 gm/cm2 Interval 0.97 to 1.18	1.24 gm/cm2 IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 4.5 months

Population: Six males with motor complete spinal cord injury (C8-T10).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Bone Formation Marker - Procollagen Type 1 N-terminal Propeptide (P1NP) in mcg/L	38 mcg/L Interval 35.0 to 45.0	53 mcg/L IQR values could not be calculated due to only 2 participants assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Four males with motor complete spinal cord injury (C8-T10)

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Bone Formation Marker - Procollagen Type 1 Intact N-Propeptide (P1NP) Measured in mcg/L	35 mcg/L Interval 34.0 to 38.5	34 mcg/L IQR values could not be calculated due to only one participant assessed within this Arm.

SECONDARY outcome

Timeframe: 4.5 months

Population: Six males with motor complete spinal cord injury (C8-T10)

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)	291 pg/mL Interval 252.5 to 393.75	512.5 pg/mL IQR values could not be calculated due to only 2 participants assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Four males with motor complete spinal cord injury (C8-T10).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX)	333 pg/mL Interval 294.0 to 367.5	306 pg/mL IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 4.5 months

Population: Six males with motor complete spinal cord injury (C8-T10).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=4 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Serum 25-hydroxyvitamin D [25(OD)D] Level	32.1 ng/mL Interval 29.2 to 38.08	37.15 ng/mL IQR values could not be calculated due to only 2 participants assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Four males with motor complete spinal cord injury (C8 to T10)

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Serum 25-hydroxyvitamin D Level	49.4 ng/mL Interval 33.2 to 49.65	50.7 ng/mL IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Four males with chronic motor-complete spinal cord injury (C8-T10).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Quality-of-life Measure: Physical Health (Scored on 1-5 Likert Scale)	75 units on a scale (0-100) Interval 65.5 to 78.0	69 units on a scale (0-100) IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Six males with motor-complete spinal cord injury (C8-T10)

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Quality-of-life Measure- Psychological Health	81 score on a scale (0-100) Interval 68.5 to 84.5	81 score on a scale (0-100) IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Six males with motor-complete spinal cord injury (C8-T10).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Quality-of-life Measure- Social Relationships Domain	69 score on a scale (0-100) Interval 62.5 to 72.0	75 score on a scale (0-100) IQR values could not be calculated due to only 1 participant assessed within this Arm.

SECONDARY outcome

Timeframe: 9 months

Population: Four males with motor complete spinal cord injury (C8 to T10).

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.

Outcome measures

Outcome measures
Measure	NMES Plus Vitamin D n=3 Participants 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=1 Participants Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Change in Quality-of-life Measure-environmental Engagement Domain	75 units on a scale (0-100) Interval 72.0 to 78.0	75 units on a scale (0-100) IQR values could not be calculated due to only 1 participant assessed within this Arm.

Adverse Events

NMES Plus Vitamin D

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Passive Movement Plus Vitamin D

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	NMES Plus Vitamin D n=4 participants at risk 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. 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 Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months	Passive Movement Plus Vitamin D n=2 participants at risk Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months 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. .
Skin and subcutaneous tissue disorders Disruption in skin integrity	25.0% 1/4 • Number of events 1 • Four weeks. This was a spontaneous reporting by the participant. The participant was followed and monitored by his SCI provider over the 4 weeks period, while research staff maintained weekly contact for updates on participant's healing process. One participant in the intervention group reported opening of an old ischial wound scar (grade II) due sitting longer than usual on a commode for routine bowel care program.	0.00% 0/2 • Four weeks. This was a spontaneous reporting by the participant. The participant was followed and monitored by his SCI provider over the 4 weeks period, while research staff maintained weekly contact for updates on participant's healing process. One participant in the intervention group reported opening of an old ischial wound scar (grade II) due sitting longer than usual on a commode for routine bowel care program.

Additional Information

Dora E. Ifon

McGuire VA Hospital

Phone: 804-675-5455

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place