Trial Outcomes & Findings for Vitamin D Supplementation and Muscle Function in Older Adults (NCT NCT02015611)

NCT ID: NCT02015611

Last Updated: 2022-11-15

Results Overview

Lower extremity muscle power will be measured at baseline, 4- and 12-month follow-up using the Nottingham Power Rig. Participants sit in a chair and unilaterally depress a foot lever attached to a flywheel as hard and as fast as they can. Power output, derived from the acceleration of the flywheel from 5 trials on each leg at maximal effort, will be recorded in Watts. Maximum leg power at baseline (from either the right or left leg) and the maximum power from the same leg at 4- and 12-month follow-up will be used in all analyses. Leg power (Watts) will be standardized to total body mass (in Kg).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 136 participants
• Primary outcome timeframe: change from baseline at 12 month follow-up reported
• Results posted on: 2022-11-15

Participant Flow

Participant milestones

Measure	Placebo Matched bottle/pill placebo Placebo: Placebo	Vitamin D 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Overall Study STARTED	70	66
Overall Study COMPLETED	65	64
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vitamin D Supplementation and Muscle Function in Older Adults

Baseline characteristics by cohort

Measure	Placebo n=70 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=66 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3	Total n=136 Participants Total of all reporting groups
Age, Continuous	73.1 years STANDARD_DEVIATION 6.3 • n=5 Participants	73.7 years STANDARD_DEVIATION 6.3 • n=7 Participants	73.4 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	32 Participants n=7 Participants	67 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	34 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants	45 Participants n=7 Participants	92 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Short Physical Performance Battery Score	7.7 score on a scale STANDARD_DEVIATION 0.2 • n=5 Participants	7.7 score on a scale STANDARD_DEVIATION 0.2 • n=7 Participants	7.7 score on a scale STANDARD_DEVIATION 0.2 • n=5 Participants

PRIMARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 4 participants in the placebo arm and 3 participants in the vitamin D arm were missing the leg power outcome at 12-month follow-up

Lower extremity muscle power will be measured at baseline, 4- and 12-month follow-up using the Nottingham Power Rig. Participants sit in a chair and unilaterally depress a foot lever attached to a flywheel as hard and as fast as they can. Power output, derived from the acceleration of the flywheel from 5 trials on each leg at maximal effort, will be recorded in Watts. Maximum leg power at baseline (from either the right or left leg) and the maximum power from the same leg at 4- and 12-month follow-up will be used in all analyses. Leg power (Watts) will be standardized to total body mass (in Kg).

Outcome measures

Measure	Placebo n=61 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=61 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in Lower Extremity Muscle Power Over 12 Months	-0.10 Watts/kg Standard Error 0.04	-0.13 Watts/kg Standard Error 0.04

PRIMARY outcome

Timeframe: over 4 months of follow-up

Population: Subset of participants from main trial with muscle biopsy at baseline and 4 months

This will be examined in muscle biopsies collected at baseline and 4-month follow-up using the ATPase, pH 9.4 technique, combined with laminin immunostaining in 10 micrometer muscle sections and the number of type I and type II fiber subtypes quantified. The percentage of type II fibers is calculated by dividing the number of type II fibers by the sum of type I and type II fibers combined.

Outcome measures

Measure	Placebo n=14 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=18 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in Percentage of Type II (Fast-twitch) Muscle Fibers Over 4 Months	-1.35 Percent of type II muscle fibers Standard Error 3.56	-3.68 Percent of type II muscle fibers Standard Error 2.81

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: Participants excluded from testing if they had ever had knee surgery, had difficulty bending/straightening either of their knees fully due to pain, arthritis, injury, or other condition, or experienced pain upon testing. At baseline, only 60 participants in the placebo group and 55 participants in the vitamin D group were able to test. At 12-month follow-up, only 50 participants in the placebo and 45 participants in the vitamin D group were able to test.

Lower extremity muscle strength will be measured using an isokinetic dynamometer (Biodex) at one speed (60°/sec) with the participant sitting and the hips and knee flexed at 90°. Participants extend the knee and push as hard as possible against the resistance pad. Strength is expressed as peak torque in Newton-meters (Nm). The maximum knee extensor strength of the 4 repetitions from trial 2 for the dominant leg will be will be used in analyses unless unable to test the dominant leg (i.e., knee replacement) in which case the non-dominant leg will be used; the maximum knee extensor strength from the same leg will be used at 4- and 12-month follow-up for all analyses.

Outcome measures

Measure	Placebo n=50 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=45 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in Lower Extremity Muscle Strength Over 12 Months	-3.84 Newton meters Standard Error 1.66	-8.09 Newton meters Standard Error 1.75

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 2 participants in the placebo group and 4 in the vitamin D group were excluded from analyses: 4 participants because they used an assistive device during testing at follow-up but not at baseline (1 in the placebo group and 3 in the vitamin D group); 1 participant because of severe knee pain and limping at follow-up (placebo group); and 1 participant was in a walking boot at 12-month follow-up (vitamin D group).

The short physical performance battery consists of standing balance (side-by-side, semi- and full-tandem stands for 10 seconds), a 4-m walk to assess usual gait speed, and 5 repeated chair stands at baseline, 4-months and 12-months. Each of the three performance measures is assigned a score ranging from 0 (inability to perform the task) to 4 (the highest level of performance) and summed to create an SPPB score ranging from 0 to 12 (best).

Outcome measures

Measure	Placebo n=63 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=60 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in the Short Physical Performance Battery (SPPB) Score Over 12 Months	1.83 score on a scale Standard Error 0.22	1.64 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 14 participants in the placebo group and 10 in the vitamin D group were excluded from analyses: 4 participants because they used an assistive device during testing at follow-up but not at baseline (1 in the placebo group and 3 in the vitamin D group); 1 participant because of severe knee pain and limping at follow-up (placebo group); 1 participant was in a walking boot at 12-month follow-up (vitamin D group); and 12 in the placebo group and 6 in the vitamin D group due to change \>2 IQR

The expanded physical performance battery consists of standing balance (semi- and full-tandem stands and a single leg stand for 30 seconds), a 4-m walk to assess usual gait speed, a narrow 4-m walk test of balance (walking at usual pace within lines of tape spaced 20 cm apart), and 5 repeated chair stands at baseline, 4-months, and 12-months. Scores range from 0 to 4 with higher scores indicative of better physical performance.

Outcome measures

Measure	Placebo n=51 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=54 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in the Expanded Physical Performance Battery Score Over 12 Months	0.17 score on a scale Standard Error 0.04	0.19 score on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 6 participants in the placebo group and 6 in the vitamin D group were excluded from analyses due to: 1 participant with foot pain (placebo group), 1 participant with knee pain and limping (placebo group), 3 participants using an aid at follow-up but not at baseline (2 placebo and 1 vitamin D group), 1 participant with vertigo (placebo group), and 6 participants with change \>2 IQR (1 placebo group, 5 vitamin D group)

The timed up and go will be measured by how long it takes (sec) to stand up from a chair, walk 3 m, turn around, walk back to the chair, and sit down at baseline, 4-months, and 12-months. Longer times to complete the TUG are indicative of greater fall risk.

Outcome measures

Measure	Placebo n=59 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=58 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in Timed Up and Go (TUG) Over 12 Months	0.98 seconds Standard Error 0.21	1.01 seconds Standard Error 0.21

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 14 participants in the placebo group and 10 in the vitamin D group were excluded from analysis: 1 participant with a foot in a walking boot (vitamin D group), 1 participant with foot pain (placebo group), 1 participant with severe knee pain (placebo group), and 12 in the placebo group and 9 in the vitamin D group due to change \>2 IQR

Postural sway during quiet stance will be assessed from Center-of-Pressure (COP) trajectory data collected at 100 Hz using an Advanced Mechanical Technology Incorporated (AMTI) AccuSway biomechanics force platform at baseline, 4-months, and 12-months. Participants stand on the force platform barefoot in an upright stance with arms relaxed comfortably at their sides, eyes open, feet abducted 10 degrees, and heels separated medio-laterally by 6 cm. COP data is collected in a series of 10 30-sec trials standing on the force plate. Average sway velocity is measured in cm/sec. A higher number indicates more postural sway.

Outcome measures

Measure	Placebo n=51 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=54 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in Average Sway Velocity Over 12 Months	0.01 cm/sec Standard Error 0.01	0.01 cm/sec Standard Error 0.01

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 14 participants in the placebo group and 10 in the vitamin D group were excluded from analysis: 1 participant with a foot in a walking boot (vitamin D group), 1 participant with foot pain (placebo group), 1 participant with severe knee pain (placebo group), and 12 in the placebo group and 9 in the vitamin D group due to change \>2 IQR

Postural sway during quiet stance will be assessed from Center-of-Pressure (COP) trajectory data collected at 100 Hz using an Advanced Mechanical Technology Incorporated (AMTI) AccuSway biomechanics force platform at baseline, 4-months, and 12-month. Participants stand on the force platform barefoot in an upright stance with arms relaxed comfortably at their sides, eyes open, feet abducted 10 degrees, and heels separated medio-laterally by 6 cm. COP data is collected in a series of 10 30-sec trials standing on the force plate. 95% confidence ellipse area is measured in cm squared. A higher number indicates more postural sway.

Outcome measures

Measure	Placebo n=51 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=54 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in 95% Confidence Ellipse Area Over 12 Months	0.00 cm squared Standard Error 0.04	0.03 cm squared Standard Error 0.04

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 14 participants in the placebo group and 10 in the vitamin D group were excluded from analysis: 1 participant with a foot in a walking boot (vitamin D group), 1 participant with foot pain (placebo group), 1 participant with severe knee pain (placebo group), and 12 in the placebo group and 9 in the vitamin D group due to change \>2 IQR

Postural sway during quiet stance will be assessed from Center-of-Pressure (COP) trajectory data collected at 100 Hz using an Advanced Mechanical Technology Incorporated (AMTI) AccuSway biomechanics force platform at baseline, 4-months, and 12-months. Participants stand on the force platform barefoot in an upright stance with arms relaxed comfortably at their sides, eyes open, feet abducted 10 degrees, and heels separated medio-laterally by 6 cm. COP data is collected in a series of 10 30-sec trials standing on the force plate. Anteroposterior (AP) displacement is measured in cm. A higher number indicates more postural sway.

Outcome measures

Measure	Placebo n=51 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=54 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in Maximum Anteroposterior (AP) Displacement Over 12 Months	0.00 cm Standard Error 0.03	0.02 cm Standard Error 0.03

SECONDARY outcome

Timeframe: change from baseline at 12 month follow-up reported

Population: 14 participants in the placebo group and 10 in the vitamin D group were excluded from analysis: 1 participant with a foot in a walking boot (vitamin D group), 1 participant with foot pain (placebo group), 1 participant with severe knee pain (placebo group), and 12 in the placebo group and 9 in the vitamin D group due to change \>2 IQR

Postural sway during quiet stance will be assessed from Center-of-Pressure (COP) trajectory data collected at 100 Hz using an Advanced Mechanical Technology Incorporated (AMTI) AccuSway biomechanics force platform at baseline, 4-months, and 12-months. Participants stand on the force platform barefoot in an upright stance with arms relaxed comfortably at their sides, eyes open, feet abducted 10 degrees, and heels separated medio-laterally by 6 cm. COP data is collected in a series of 10 30-sec trials standing on the force plate. Mediolateral (ML) displacement is measured in cm. A higher number indicates more postural sway.

Outcome measures

Measure	Placebo n=51 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=54 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Change in Maximum Mediolateral (ML) Displacement Over 12 Months	-0.01 cm Standard Error 0.04	0.06 cm Standard Error 0.04

OTHER_PRE_SPECIFIED outcome

Timeframe: monthly over 12 months

Population: 1 participant in the placebo group and 4 participants in the vitamin D group did not return their falls calendar

Falls will be defined as an event whereby an individual unexpectedly comes to rest on the ground or another lower level. Participants will be provided monthly fall calendars and asked to mark any falls that occur on the calendar. Completion of monthly fall calendars will be monitored via monthly phone calls and collected at the 4- and 12-month visits. The number of total falls per participant over the entire 12-month follow-up period will be used in analysis.

Outcome measures

Measure	Placebo n=64 Participants Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=60 Participants 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Number of Falls Over 12 Months	1.47 number of falls Standard Deviation 2.76	1.40 number of falls Standard Deviation 2.85

Adverse Events

Placebo

Serious events: 12 serious events

Other events: 29 other events

Deaths: 0 deaths

Vitamin D

Serious events: 6 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=70 participants at risk Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=66 participants at risk 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Gastrointestinal disorders Hospitalization	2.9% 2/70 • Number of events 2 • 12 months	0.00% 0/66 • 12 months
Cardiac disorders Hospitalization	2.9% 2/70 • Number of events 2 • 12 months	1.5% 1/66 • Number of events 1 • 12 months
Blood and lymphatic system disorders Hospitalization	1.4% 1/70 • Number of events 1 • 12 months	0.00% 0/66 • 12 months
Ear and labyrinth disorders Hospitalization	0.00% 0/70 • 12 months	1.5% 1/66 • Number of events 1 • 12 months
Immune system disorders Hospitalization	1.4% 1/70 • Number of events 1 • 12 months	0.00% 0/66 • 12 months
Hepatobiliary disorders Hospitalization	0.00% 0/70 • 12 months	1.5% 1/66 • Number of events 1 • 12 months
Infections and infestations Hospitalization	4.3% 3/70 • Number of events 4 • 12 months	3.0% 2/66 • Number of events 3 • 12 months
Injury, poisoning and procedural complications Life threatening illness or accident	1.4% 1/70 • Number of events 1 • 12 months	0.00% 0/66 • 12 months
Musculoskeletal and connective tissue disorders Hospitalization	2.9% 2/70 • Number of events 2 • 12 months	3.0% 2/66 • Number of events 4 • 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hospitalization	1.4% 1/70 • Number of events 1 • 12 months	0.00% 0/66 • 12 months
Nervous system disorders Hospitalization	0.00% 0/70 • 12 months	1.5% 1/66 • Number of events 1 • 12 months
Renal and urinary disorders Hospitalization	1.4% 1/70 • Number of events 3 • 12 months	0.00% 0/66 • 12 months
Surgical and medical procedures Hospitalization	2.9% 2/70 • Number of events 2 • 12 months	1.5% 1/66 • Number of events 3 • 12 months
Vascular disorders Hospitalization	0.00% 0/70 • 12 months	1.5% 1/66 • Number of events 1 • 12 months
Injury, poisoning and procedural complications Hospitalization	0.00% 0/70 • 12 months	1.5% 1/66 • Number of events 1 • 12 months

Other adverse events

Measure	Placebo n=70 participants at risk Matched bottle/pill placebo Placebo: Placebo	Vitamin D n=66 participants at risk 2,000 IU Vitamin D3 per day Vitamin D: 2,000 IU/ day of Vitamin D3
Musculoskeletal and connective tissue disorders Arthritis	14.3% 10/70 • Number of events 10 • 12 months	4.5% 3/66 • Number of events 3 • 12 months
Musculoskeletal and connective tissue disorders Back pain	7.1% 5/70 • Number of events 5 • 12 months	6.1% 4/66 • Number of events 5 • 12 months
Injury, poisoning and procedural complications Fall	11.4% 8/70 • Number of events 10 • 12 months	9.1% 6/66 • Number of events 6 • 12 months
Infections and infestations Urinary tract infection	8.6% 6/70 • Number of events 8 • 12 months	4.5% 3/66 • Number of events 3 • 12 months

Additional Information

Dr. Denise Houston

Wake Forest University School of Medicine

Phone: 336-713-8217

Email: dhouston@wakehealth.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place