Clinical trial NCT02066441: Vitamin D's Effect on Physical Performance in the Elderly
Official title: The Effect of Vitamin D on Serum Vitamin D Levels, Bone Formation, Resorption, and Mineral Density, Inflammation, Flexibility, and Balance in the Elderly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Family Member
Keywords: Vitamin D
bone formation
resorption
mineral density
inflammation
flexibility
balance
elderly
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Biotics, Inc.
First posted: 2014-02-19
Enrollment: 101
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to compare vitamin D deficient and vitamin D sufficient elderly individuals and examine the effect of a vitamin D dietary supplement on serum vitamin D level, bone formation, resorption, and mineral density, flexibility, balance, general inflammation,and quality of life. Enhancing nutritional status is necessary to prevent the continued proliferation of chronic diseases, e.g., bone disease and other chronic disorders thought to now be related to low levels of vitamin D, which are some of the leading disablers and killers of Americans. Americans also have difficulties with compliance to prescription medications due to their toxicity and side effects. This study aims to learn more about how a vitamin D nutritional supplement may improve nutritional status and enable the body to normalize system functioning,which may improve the quality of life for people with vitamin D deficiency. The results of this research will be used to determine if vitamin D is beneficial for overall health among elderly individuals.

Detailed description: The proposed study has two parts and is observational (first part) and experimental (second part) in design. The purpose of the first part of this study is a cross-sectional investigation of the relationship among vitamin D status, vitamin D intake and sun exposure, and physical performance in 130 community dwelling older adult (≥55 years old). The purpose of the second part of the study is a 6-month, randomized, double-blind, placebo-controlled trial to evaluate the effect of vitamin D supplementation (Bio-D-Mulsion Forte®) for improving physical performance, serum levels of 25-OH-vitamin D, PTH, bone formation (osteocalcin), bone resorption (type 1 cross linked C telopeptide (CTX)), and bone mineral density (dual energy x-ray absorptiometry in a sub-sample of 20 participants) in 40 participants (≥55 years of age) who are vitamin D insufficiency at baseline (\<30 ng/ml serum 25(OH)D). Secondary outcomes will include body composition, lower back/hamstring flexibility, balance, gustatory response to the treatment, general inflammation, quality of life, depression, fear of falling, history of falls, and food security. Information on sun exposure, vitamin D and calcium intake, physical activity level, and reflectance calorimetry will also be collected. Participants will be assessed at baseline and 6-months follow-up. This part of the study will consist of two treatment arms: (a) vitamin D dietary nutritional supplement and (b) placebo.

The primary risk for the placebo group is that they will show no improvement in serum levels of 25-OH-vitamin D, bone formation, bone resorption, bone mineral density, and secondary outcomes associated with vitamin D supplementation. However, they are not being restricted in any way to receive vitamin D through sunlight exposure and their food. Each participant in the placebo group will also receive a 6-month supply of the vitamin D supplement (Bio-D-Mulsion Forte®) at the conclusion of their participation in the study. Additionally, the risk of placebo is also offset by the knowledge gained from actually receiving a serum level 25-OH-vitamin D score at baseline and 6-months follow-up, which is not typically assessed by the average provider. Finally, the short-term period of the study does not increase long-term health risks associated with the study, as other studies have utilized placebo-controlled trials with vitamin D deficient adults previously and have observed no adverse effects . Normal serum levels of 25-OH-vitamin D can be achieved within 2-5 months according to the literature.

The health risks associated with consuming a vitamin D dietary supplement are inconclusive. Hypercalcemia is one potential adverse effect, but according to one review no increases in mean calcium levels occurred with higher vitamin D intakes tested in controlled trials up to 100,000 IU per day. For single cases of hypercalcemia from randomized controlled trials, cases of mild hypercalcemia were reported in 2 of 28 studies, which resolved on repeating fasting samples in one study and were actually more frequent in the placebo group in the other study. Additionally, hypercalcemia has been mostly found in cases of persons with serum levels of 25(OH)D greater than 240 nmol/L.

An increased risk of nephrolithiasis was found in one randomized controlled trial (the Women's Health Initiative (WHI)), which tested 400 IU vitamin D in combination with 1000 mg of calcium. The reason for nephrolithiasis in this study is unclear; factors include: (1) this study may have been large enough to detect a small risk of nephrolithiasis with vitamin D supplementation; (2) nephrolithiasis was caused by the calcium supplement intake taken in combination with the vitamin D as part of the protocol; and/or (3) the nephrolithiasis was caused by the additional calcium and vitamin D supplements taken by the majority of participants outside the study protocol. The low dose of vitamin D used in the WHI argues against a causal role of the increased risk of nephrolithiasis. Based on epidemiologic data, a higher vitamin D intake was not independently associated with nephrolithiasis in one large cohort consistent with findings from a recent study of 18 healthy postmenopausal women with vitamin D deficiency where vitamin D supplementation did not increase urinary calcium excretion. On the other hand, calcium supplementation was associated with a 20% increased risk of nephrolithiasis in the Nurses Health Study I.

The issue of vascular calcification has also been noted as a potential risk of vitamin D supplementation. However, reports in the literature continue to be restricted to extremely high doses of vitamin D3 or administration of the active hormonal form, 1,25(OH)2D3 and/or related analogues, and most of these reports are in animals, not humans. No credible evidence exists to support the notion that oral vitamin D doses up to and even exceeding 10,000 IU per day are associated with vascular calcification in humans, including dialysis patients, and no basis exists for identifying vascular calcification as a critical effect.

Participants may experience discomfort while answering the questionnaires and while undergoing the venipuncture, but they may stop the assessments at any time. Although all measures to protect confidentiality will be put in place, the possibility exists that electronic data could be jeopardized. In the remote case that such event occurs, it will be immediately reported to the IRB.

The vitamin D dietary supplement should be harmless without any food allergy or sensitivity. No episodes of side effects have been reported to Biotics Research Corporation, the manufacturer, by consumers in the previous 5 years.

A toxicology search for each component reveals no unique toxicity characteristic of the materials. As reported by Biotics Research Corporation, thousands of people currently use Bio-D-Mulsion Forte®, and Biotics Research Corporation is unaware of significant toxicities. A major concern with raw natural products is the presence of contaminants.

Biotics Research Corporation operates in accordance with D-SHEA regulations, and Bio-D-Mulsion Forte® is made of the highest purity, quality, and potency. Biotics Research Corporation manufacturers their products under strict GMP guidelines in an FDA-registered facility, is licensed by the Texas Department of State Health Services Regulatory Licensing Unit as a Food and Non-prescription Drug Manufacturer, and is licensed by Health Canada (Site License) and is considered to be in compliance with the GMP requirements of their Natural Health Products Regulations. Biotics Research Corporation conducts multiple quality control tests on all of its products.

Participants will incur no additional appreciable psychological or social risks by participating in this study, although they may undergo psychological and physical discomfort sometimes. The process of interviewing during the assessment may cause discomfort. Discomfort or fatigue may also be experienced in completing the assessment battery.

Alternatives to this study include prescription medications, sun exposure, exercise, dietary modification, and other nutritional supplements. The risks of medications can be very significant, including life-threatening, but the risk of taking nutritional supplements is not totally understood, since they are not regulated by the FDA. Medications and nutritional supplements, as part of a change in lifestyle behaviors, may also prove to be beneficial for improving serum vitamin D levels, but their long-term use has unknown consequences.

The information obtained in this study will help in determining the efficacy of using a dietary supplement for improving serum vitamin D levels. By participating in the study, subjects may experience improved serum vitamin D level, bone formation, bone resorption, bone mineral density according to DEXA scan, flexibility, balance, and quality of life, while reducing their risk for other diseases. The risk of participating in this study is reasonable because the improvements in serum vitamin D level, bone formation, bone resorption, bone mineral density, flexibility, balance, gustatory response to the treatment, general inflammation, and quality of life associated with improved nutritional status will be enhanced.

The investigators are looking at an older population due to changes in all of our outcomes that are typically associated with aging. No consensus exists on what age is considered elderly, but the investigators have chosen 55 to have a wider age range. Other investigators have used non-elderly participants with a similar or higher dose of vitamin D supplementation.

Eligibility criteria: Inclusion Criteria:

* Men and women ages 55 years and over
* English or Spanish speaking
* Interest in participating in a novel nutritional supplement program
* Willingness to follow recommendations, including going off of all vitamin-D and calcium containing supplements, multivitamins, or OTC medications (e.g., Tums) 2 weeks before starting the study and during the intervention
* Scoring 0-2 errors on the Short Portable Mental Status Questionnaire

Exclusion Criteria:

* Less than 55 years of age
* Currently enrolled in another research trial for vitamin D dietary supplements or other bone disease treatments
* Unable to consent to the study
* Living in a skilled or intermediate care level nursing facility
* Women who are pregnant, during their period, or less than 2 days before or after their period at the time of the assessment
* Psychiatric diagnosis of schizophrenia, other psychotic disorders, bipolar disorder, major depression with psychotic features, delirium, and alcohol or substance abuse/dependence
* Bleeding disorders
* Aphasia or sensory, motor, and/or visual disturbances that could interfere with assessments, including inability to walk 10 feet without a walking aid
* Gastrointestinal disorders that could lead to uncertain resorption of the study supplements
* Major conditions such as neurologic, cardiovascular, pulmonary, renal, endocrine, thyroid, hepatic, autoimmune, or bone/joint that could interfere with vitamin D metabolism, psychometric tests, or body composition assessment (especially renal and heart failure)
* Erratic, accelerated, or mechanically-controlled irregular heart rhythms, atrial fibrillation/flutter, or atrioventricular block or implanted electronic device
* Any condition restricting blood flow, such as severe systemic vascular resistance
* Acute fever, diarrhea, or edema at the time of the assessment
* Dermatological lesions or excessive hair that would be in contact with the placement of the electrodes for the ESC assessment
* Hematologic or oncologic disorders treated with chemotherapy in the previous two years
* Dysfunctional levels of hemoglobins like carboxyhemoglobin or methemoglobin
* Active chemotherapy or radiation treatment for cancer
* Recent infusion of dyes into the bloodstream such as methylene blue, indocyanine green, indigo carmine, or fluorescein
* Diagnosis of a terminal illness
* Persons may not be in the second part of the study while participating in another trial for drugs, supplements, or treatment that affects serum vitamin D level
* Persons may not be in the second part of the study if they are unwilling to go off all vitamin D and calcium containing supplements, multivitamins, and over the counter medications 2 weeks prior to starting the study and for the duration of the second part of the study
* Persons may not be in this study if they are unwilling to have their blood drawn
* Persons may not be in the second part of the study if they are taking steroids, HCTZ, or any other drug known to interfere with vitamin D metabolism or taking diuretics or any other drug that interferes with hydration status
* Persons may not be in this study if they are unwilling to refrain from alcohol, caffeine, and stimulants (amphetamines) 12 hours before the examination
* Persons may not be in this study if they are unwilling to stop physical activity or sauna use 8 hours before the examination
* Persons may not be in this study if they are unwilling to remove fingernail polish or false fingernails during the testing

Primary outcomes:
measure: Change from Baseline in Serum 25-(OH) D level at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Serum parathyroid hormone (PTH) levels at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Serum Osteocalcin at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Serum CTX at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Serum C-reactive Protein at 6 months
timeFrame: Baseline, 6 months
Secondary outcomes:
measure: Change from Baseline in Systolic Blood Pressure at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Diastolic Blood Pressure at 6 months
timeFrame: Baseline, 6 months
measure: Pulse
timeFrame: Baseline, 6 months
measure: Change from Baseline in Gait Velocity at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Step Length at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Base of Support at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Single Support Time at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Double Support Time at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Balance and Physical Performance at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Flexibility at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Physical Activity at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Vitamin D and Calcium intake at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Food Security at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Sun Exposure at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Quality of Life at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Depression at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Fear of Falling at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Fall Frequency at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Compliance at 6 months
timeFrame: Baseline, 6 months
measure: Change from Baseline in Skin Color due to Sun Exposure at 6 months
timeFrame: Baseline, 6 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Clinical Research Building
state: Florida
Study officials:
affiliation: University of Miami
name: John Lewis, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chandra P, Binongo JN, Ziegler TR, Schlanger LE, Wang W, Someren JT, Tangpricha V. Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study. Endocr Pract. 2008 Jan-Feb;14(1):10-7. doi: 10.4158/EP.14.1.10.
citation: Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001 Feb;73(2):288-94. doi: 10.1093/ajcn/73.2.288.