Vitamin D Supplementation and Muscle Function in Older Adults (EVIDENCE)

Trial of Vitamin D Supplementation and Neuromuscular Function in Older Adults

The purpose of this study is to see if vitamin D supplementation improves muscle function in older adults.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Function
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Vitamin D

Detailed Description

This study is a 12-month, double-blind randomized placebo controlled trial in older (65-89 yrs) men and women with initial 25(OH)D concentrations of 18-<30 ng/mL to determine the effect of increasing 25(OH)D concentrations to ≥30 ng/mL through vitamin D3 supplementation on 1) change in neuromuscular functions that are established risk-factors for falls in older adults; and 2) changes in the underlying physiological mechanisms over 4 months in a subset of randomly selected participants. Participants will be randomized to 2000 IU/d of vitamin D3 or placebo. Lower extremity muscle strength and power, physical performance, and postural sway will be assessed at baseline, 4 months and 12 months and falls assessed monthly. Muscle biopsies of the vastus lateralis will be taken at baseline and 4 months to assess muscle fiber type, contractility, and denervation, and number and differentiation stage of satellite cells.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 89 years (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥65 to <90 years
• SPPB <=10
• Initial serum 25(OH)D concentration of 18 to <30 ng/mL
• Not dependent on a walker
• Able to provide own transportation to study visits
• Not involved in another intervention study
• Willing to provide informed consent and adhere to the protocol

Exclusion Criteria:

• Serious or uncontrolled chronic disease including: insulin-dependent diabetes; cancer requiring treatment in past year, except non-melanoma skin cancers; acute coronary event (within the last 6 months), uncontrolled angina, heart failure (stage 3-4), PAD, or stroke (within the last 6 months); uncontrolled hypertension (BP>200/110 mmHg); chronic respiratory disease requiring the use of oxygen; uncontrolled endocrine/metabolic disease; neurological (e.g., Parkinson's disease) or hematological disease; liver or renal dysfunction (eGFR <45 mL/min/1.73m2); and musculoskeletal impairments severe enough to preclude functional testing
• Evidence of impaired cognitive function (MoCA <18)
• Taking prescription vitamin D2 or taking >1000 IU/day of vitamin D3 (from all sources); taking an oral corticosteroid (i.e., prednisone at 7.5mg/d for 3 mos or equivalent); taking hormone replacement therapy
• Inability or contraindications to consume daily vitamin D supplements (e.g., hypercalcemia, sarcoidosis, history of kidney stones in last 5 years)
• Knee or hip surgery within the last 6 months or planned knee or hip surgery within the next year
• Unwillingness to undergo a muscle biopsy or use of anti-coagulants
• Unintentional weight loss of ≥5% or more in the past 3 months
• BMI >40 kg/m2
• If the PI feels the participant is unlikely to follow the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matched bottle/pill placebo	Dietary supplement: Placebo; Placebo
Experimental: Vitamin D; 2,000 IU Vitamin D3 per day	Dietary supplement: Vitamin D; 2,000 IU/ day of Vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Lower Extremity Muscle Power Over 12 Months	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).	change from baseline at 12 month follow-up reported
Change in Percentage of Type II (Fast-twitch) Muscle Fibers Over 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.	over 4 months of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Lower Extremity Muscle Strength Over 12 Months	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.	change from baseline at 12 month follow-up reported
Change in the Short Physical Performance Battery (SPPB) Score Over 12 Months	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).	change from baseline at 12 month follow-up reported
Change in the Expanded Physical Performance Battery Score Over 12 Months	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.	change from baseline at 12 month follow-up reported
Change in Timed Up and Go (TUG) Over 12 Months	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.	change from baseline at 12 month follow-up reported
Change in Average Sway Velocity Over 12 Months	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.	change from baseline at 12 month follow-up reported
Change in 95% Confidence Ellipse Area Over 12 Months	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.	change from baseline at 12 month follow-up reported
Change in Maximum Anteroposterior (AP) Displacement Over 12 Months	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.	change from baseline at 12 month follow-up reported
Change in Maximum Mediolateral (ML) Displacement Over 12 Months	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.	change from baseline at 12 month follow-up reported

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Falls Over 12 Months	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.	monthly over 12 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Aging (NIA); Office of Dietary Supplements (ODS)
• Investigators: Principal Investigator: Denise K Houston, PhD, RD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): September 26, 2018
• Study Completion (Actual): September 26, 2018

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Vitamin D; Aging; Falls; Muscle power; Muscle fiber
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: IRB00022395; R01AG042411 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No