A Pilot Study to Examine the Effects of Vitamin D Supplementation on Mitochondrial Bioenergetics in Older Adults

August 13, 2018 updated by: Wake Forest University Health Sciences

A Pilot Study to Examine the Effects of Vitamin D Supplementation on Mitochondrial Bioenergetics in Older Adults - An EVIDENCE Sub-Study

This pilot study is a 4-month open label trial in 15 older (65-89 yrs) men and women with initial 25(OH)D concentrations of 12-<18 ng/mL to explore the effect of increasing 25(OH)D concentrations to ≥30 ng/mL through vitamin D3 supplementation on changes in mitochondrial bioenergetics. We will assess the bioenergetic profile of blood cells isolated mitochondria, and muscle fibers as well as the expression of mitochondrial proteins and regulators of mitochondria biogenesis before and after supplementation. All participants will be given vitamin D3 (4,000 IU/d) for 4 months.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In the past two decades, the role of vitamin D has extended beyond bone health to encompass a wide range of biological activities important to muscle function in older adults. Low 25-hydroxyvitamin D (25[OH]D) concentrations (<30 ng/mL) are associated with lower extremity muscle weakness, impaired physical performance, and slower walking speed,(1-8) known risk factors for disability.(9-15) Low 25(OH)D concentrations in older adults have also been associated with frailty as well as the individual frailty components including muscle weakness, slow walking speed, and exhaustion/fatigue.(16-18) Clinical findings of vitamin D deficiency (25(OH)D <12 ng/mL) include proximal muscle weakness, muscle pain, and gait impairments which are often reversed with vitamin D supplementation.(19;20) However, vitamin D's effects on the mechanisms underlying muscle function are not well understood. Recent evidence supports a role for vitamin D in skeletal muscle mitochondrial metabolism. Using 31P-MRS imaging, an increase in maximal mitochondrial oxidative phosphorylation (OXPHOS) has been reported following vitamin D supplementation.(21) Thus, we hypothesize that muscle weakness and slow walking speed in individuals with low 25(OH)D concentrations may in part be due to diminished OXPHOS activity and lower ATP generation in skeletal muscle mitochondria.

Vitamin D insufficiency is common in older adults, ranging from approximately one-third to three-fourths of community-dwelling adults aged ≥70 years depending on the cut-point used (25(OH)D <20 ng/mL or <30 ng/mL, respectively).(22;23) Similarly, bioenergetic decline is broadly associated with increasing age.(24) Thus, examining the association between vitamin D and mitochondrial bioenergetics can improve our understanding of the underlying mechanisms and range of potential benefits of remediating low 25(OH)D concentrations in older adults.

The objective of the study is to obtain preliminary data on the effect of increasing 25(OH)D concentrations among older adults with vitamin D insufficiency to ≥30 ng/mL through vitamin D3 supplementation on 1) bioenergetic profiles of multiple blood cell populations, skeletal muscle mitochondria, and muscle fibers and 2) skeletal muscle mitochondrial mass and biogenesis.

Hypothesis 1: Bioenergetic capacity as well as respiratory control in muscle mitochondria, muscle fibers, and blood cells will be improved following 4 months of vitamin D3 supplementation.

Hypothesis 2: Expression of key mitochondrial proteins (VDAC/Porin and COX4) and regulators of mitochondria biogenesis (PGC1a, SIRT1, SIRT3, and TFAM) will be higher following 4 months of vitamin D3 supplementation.

We plan to recruit individuals only from screen fails of the EVIDENCE study (IRB00022395). The EVIDENCE study is enrolling 200 participants whose 25(OH)D concentrations are 18-<30 ng/mL. Those whose concentrations are 12-<18 ng/mL at their EVIDENCE screening visit will be approached about participating in this pilot study. We will utilize the EVIDENCE screen fails because this is a pilot study with limited funding, the screening labs (25(OH)D) are expensive and the number needed to screen would be cost-prohibitive in a pilot study, and these two studies are run in the same clinic with the same staff. All screening measures will occur during the EVIDENCE study and measures will begin for this study at the baseline visit.

All persons who screen fail for EVIDENCE with a 25(OH)D concentration of 12-<18 ng/mL will be informed that they are not eligible for the EVIDENCE study and will be called with these results. If they meet all of the same eligibility criteria for this study which eliminates participants with conditions that may affect their ability to safely perform the neuromuscular function tests, consume vitamin D supplements, or undergo a muscle biopsy, these people will be informed that we have another study for those whose vitamin D levels are insufficient. If interested, they will be asked to come in for a baseline visit (as long as this visit can occur within 2 months of their EVIDENCE screening visit). Those persons who screened more than 2 months ago for the EVIDENCE study will not be eligible for this study as the lab work and other tests performed may no longer be accurate.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 89 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • SPPB score of 10 or less
  • initial serum 25(OH)D concentration of 12-17.9 ng/mL
  • not dependent on a walker
  • willing to provide informed consent and to adhere to the protocol
  • not involved in another behavioral, exercise, or investigational drug intervention study
  • self-reported physical performance difficulty
  • were screened for the EVIDENCE study within the last 2 months

Exclusion Criteria:

  • serious or uncontrolled chronic disease
  • 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; taking hormone replacement therapy
  • inability or contraindications to consume daily vitamin D supplements
  • knee or hip surgery within the last 6 months or planned knee or hip surgery within the next year
  • not willing or eligible to undergo a muscle biopsy (on blood thinners)
  • weight loss of greater than or equal to 5% in the past 3 months
  • BMI > 40kg/m2
  • eye surgery within the past month or planned within the next month
  • if the PI feels the participant is unlikely to follow the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Open label
Vitamin D3 - 4,000 IU/day for 4 months
Dietary supplement: Vitamin D3

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Respirometric profiling
Time Frame: 4 months
Respirometry of isolated mitochondria will be performed in order to examine intrinsic mitochondrial function (type1). Respirometry of permeabilized muscle fibers will be performed to assess type 2 alterations in mitochondrial function. Mitochondrial mass and biogenesis will be determined by western blot analysis. Blood based bioenergetic profiling - PBMC's, monocytes, lymphocytes, and platelets will be separated from whole blood and assessed for basal respiration, maximal respiration, ATP linked respiration, spare respiratory capacity, proton leak, and non-mitochondrial respiration.
4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Lower extremity muscle power
Time Frame: 4 months
The Nottingham Power Rig will be used for assessing power output from the lower limbs. Participants sit in a chair and unilaterally depress a foot lever, which is attached to a flywheel, as hard and as fast as they can. Power output, derived from the acceleration of the flywheel, will be recorded in Watts.
4 months
Physical performance
Time Frame: 4 months
Physical performance will be assessed using the expanded Short Physical Performance Battery, the Timed Up and Go tests, and Usual and Fast walking speeds over 20 meters.
4 months
Grip strength
Time Frame: 4 months
Grip strength will be measured using an isometric hydraulic hand dynamometer (Jamar, Bolingbrook, IL)
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wake Forest University Health Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anthony Molina, PhD, Wake Forest University Health Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 11, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 15, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 15, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00028235

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Low 25-hydroxyvitamin D Concentrations

Clinical Trials on Vitamin D3

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings