Clinical trial NCT02166333: Study To Understand Fall Reduction and Vitamin D in You
Official title: Vitamin D Supplements to Prevent Falls in Older Adults: A Dose-Response Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Vitamin D Deficiency
Falls
Keywords: vitamin D
falls
high risk of falling
insufficient or deficient serum vitamin D levels
10-29 ng/ml
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2014-06-18
Enrollment: 688
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Vitamin D supplements might substantially reduce the risk of falls, potentially by more than 25%. The proposed study is a clinical trial that will determine the effects of 4 doses of vitamin D (200 International Units \[IU\]/day, 1000 IU/day, 2000 IU/d and 4000 IU/d) as a means to prevent falls in high-risk adults, ages 70 and older. Results of this trial will be directly relevant to public health and clinical guidelines, and will immediately influence policy.

Detailed description: The public health burden of falls in older persons is substantial. Several lines of evidence suggest that vitamin D supplements might reduce the risk of falls, potentially by 25% or more in persons with low serum 25-hydroxyvitamin D \[25(OH)D\] levels. However, existing evidence is inconsistent and insufficient to guide policy. The trial is a seamless two-stage, Bayesian response-adaptive, randomized dose-finding trial designed to select the best dose of vitamin D supplementation and to potentially confirm the efficacy of that dose for fall prevention and other related outcomes. Participants will be community-dwelling adults, aged 70+ (goal of \~40% black, \~60% women), with a baseline serum 25(OH)D level of 10-29 ng/ml, who are at high risk for falling.

In Stage 1 of the adaptive design, participants will be randomly assigned to one of four vitamin D3 (cholecalciferol) doses: 200 IU/d (control), 1000 IU/d, 2000 IU/d, or 4000 IU/d, with assignment probabilities that will vary as falls are reported. Participants will take their assigned pills for two years, or until the study ends, whichever comes first. This stage of the design will select the best non control dose of vitamin D for prevention of falls, or confirm the futility of distinguishing any differences among the non control doses for fall prevention. If a best dose is selected, subsequent participants will be randomized in Stage 2 of the trial into the comparison (200 IU/d) or best dose group, and all participants (Stage 1 and Stage 2) will continue to be followed to potentially confirm efficacy. The investigators anticipate enrolling approximately 1,200 participants over the entire length of the project.

The primary outcome is time to first fall (or death) over two years of therapy. Next in importance is the outcome of gait speed. Other outcomes include fall rates, types of falls, balance, muscle strength, frailty, Short Physical Performance Battery (SPPB) score, 6-minute walk time, and physical activity assessed by accelerometry. Falls will be ascertained from fall calendars completed daily by participants and from self-report by phone. In-person follow-up visits will occur at 3, 12, and 24 months, with telephone visits occurring at 1, 6, 9, 15, 18, and 21 months after randomization. Subgroups with potential for greater benefit from vitamin D supplementation are blacks, those with baseline 25(OH)D of 10-19 ng/ml, and those with objective evidence of low physical function.

Eligibility criteria: Inclusion Criteria:

* Age 70 and older
* Non-institutionalized
* High risk for falling, defined by a 'yes' response to at least one of the following:
* 1. Have you fallen and hurt yourself in the past year?
* 2. Have you fallen 2 or more times in the past year?
* 3. Are you afraid that you might fall because of balance or walking problems?
* 4. Do you have difficulty maintaining your balance when bathing, dressing, or getting in and out of a chair?
* 5. Do you use a cane, walker, or other device when walking inside or outside your home?
* Serum vitamin D \[25(OH)D\] level of 10-29 ng/ml
* Able to provide informed consent
* Willing to accept randomization to each vitamin D dose
* One of the following:
* 1. No vitamin D supplementation at baseline
* 2. Average daily vitamin D supplementation judged by study staff as being consistent with the goal of 1000 IU/day or less at screening and willing to continue the dose unchanged throughout the trial
* One of the following:
* 1. No calcium supplementation at baseline
* 2. Average daily calcium supplementation judged by study staff as being consistent with the goal of 1200 mg/day or less at screening and willing to continue the dose unchanged throughout the trial

Exclusion Criteria:

* Cognitive impairment, defined by Mini-Mental State Exam (MMSE) score \<24
* Hypercalcemia, serum Ca++ 11.0 mg/dl or higher or \>10.5 mg/dl (confirmed)
* Hypocalcemia, serum Ca++ \<8.5 mg/dl
* Kidney, ureteral, or bladder stones made of calcium compounds (2 or more in lifetime, or 1 in the last 2 years); in the absence of information on the type of stone, stones will be assumed to be made of calcium compounds
* Planning to move out of area within 2 years, where plans would prevent compliance with the study protocol
* Disease or condition expected to cause death or to prevent compliance with the study protocol in the next 2 years
* Participation in another trial of vitamin D or falls, or any trial that might affect the risk of falls
* Lactose allergy (lactose intolerance is okay)
* Use of any form of oral or injected calcitriol (brand names: Rocaltrol (R), Calcijex (R), and Zemplar (R); generic names: calcitriol, paricalcitol, doxycalcitriol, 22-oxacalcitriol)

Primary outcomes:
measure: Incidence of First Fall or Death (Whichever Comes First)
timeFrame: Randomization to 24 months or end of trial, whichever came first
Secondary outcomes:
measure: Change in Gait Speed
timeFrame: Baseline, 3 months, 12 months and 24 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: ProHealth Clinical Research Unit
state: Maryland
city: Hagerstown
country: United States
facility: Comstock Center for Public Health Research and Prevention
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Lawrence J Appel, MD, MPH
role: STUDY_CHAIR
References:
citation: Michos ED, Kalyani RR, Blackford AL, Sternberg AL, Mitchell CM, Juraschek SP, Schrack JA, Wanigatunga AA, Roth DL, Christenson RH, Miller ER 3rd, Appel LJ. The Relationship of Falls With Achieved 25-Hydroxyvitamin D Levels From Vitamin D Supplementation: The STURDY Trial. J Endocr Soc. 2022 Apr 16;6(6):bvac065. doi: 10.1210/jendso/bvac065. eCollection 2022 Jun 1.
citation: Juraschek SP, Appel LJ, M Mitchell C, Mukamal KJ, Lipsitz LA, Blackford AL, Cai Y, Guralnik JM, Kalyani RR, Michos ED, Schrack JA, Wanigatunga AA, Miller ER 3rd. Comparison of supine and seated orthostatic hypotension assessments and their association with falls and orthostatic symptoms. J Am Geriatr Soc. 2022 Aug;70(8):2310-2319. doi: 10.1111/jgs.17804. Epub 2022 Apr 22.
citation: Cai Y, Wanigatunga AA, Mitchell CM, Urbanek JK, Miller ER 3rd, Juraschek SP, Michos ED, Kalyani RR, Roth DL, Appel LJ, Schrack JA. The effects of vitamin D supplementation on frailty in older adults at risk for falls. BMC Geriatr. 2022 Apr 10;22(1):312. doi: 10.1186/s12877-022-02888-w.
citation: Guralnik JM, Sternberg AL, Mitchell CM, Blackford AL, Schrack J, Wanigatunga AA, Michos E, Juraschek SP, Szanton S, Kalyani R, Cai Y, Appel LJ; STURDY Collaborative Research Group. Effects of Vitamin D on Physical Function: Results From the STURDY Trial. J Gerontol A Biol Sci Med Sci. 2022 Aug 12;77(8):1585-1592. doi: 10.1093/gerona/glab379.
citation: Miller HN, Plante TB, Gleason KT, Charleston J, Mitchell CM, Miller ER 3rd, Appel LJ, Juraschek SP. A/B design testing of a clinical trial recruitment website: A pilot study to enhance the enrollment of older adults. Contemp Clin Trials. 2021 Dec;111:106598. doi: 10.1016/j.cct.2021.106598. Epub 2021 Oct 12.
citation: Juraschek SP, Miller ER, Wanigatunga AA, Schrack JA, Michos ED, Mitchell CM, Kalyani RR, Appel LJ. Effects of Vitamin D Supplementation on Orthostatic Hypotension: Results From the STURDY Trial. Am J Hypertens. 2022 Feb 1;35(2):192-199. doi: 10.1093/ajh/hpab147.
citation: Appel LJ, Michos ED, Mitchell CM, Blackford AL, Sternberg AL, Miller ER 3rd, Juraschek SP, Schrack JA, Szanton SL, Charleston J, Minotti M, Baksh SN, Christenson RH, Coresh J, Drye LT, Guralnik JM, Kalyani RR, Plante TB, Shade DM, Roth DL, Tonascia J; STURDY Collaborative Research Group. The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults : A Response-Adaptive, Randomized Clinical Trial. Ann Intern Med. 2021 Feb;174(2):145-156. doi: 10.7326/M20-3812. Epub 2020 Dec 8.
citation: Plante TB, Gleason KT, Miller HN, Charleston J, McArthur K, Himmelfarb CD, Lazo M, Ford DE, Miller ER 3rd, Appel LJ, Juraschek SP; STURDY Collaborative Research Group. Recruitment of trial participants through electronic medical record patient portal messaging: A pilot study. Clin Trials. 2020 Feb;17(1):30-38. doi: 10.1177/1740774519873657. Epub 2019 Oct 3.
citation: Michos ED, Mitchell CM, Miller ER 3rd, Sternberg AL, Juraschek SP, Schrack JA, Szanton SL, Walston JD, Kalyani RR, Plante TB, Christenson RH, Shade D, Tonascia J, Roth DL, Appel LJ; STURDY Collaborative Research Group. Rationale and design of the Study To Understand Fall Reduction and Vitamin D in You (STURDY): A randomized clinical trial of Vitamin D supplement doses for the prevention of falls in older adults. Contemp Clin Trials. 2018 Oct;73:111-122. doi: 10.1016/j.cct.2018.08.004. Epub 2018 Aug 20.