Prevention of Falls and Fractures in Old People by Administration of Calcium and Vitamin D. Randomized Clinical Trial (ANVITAD)

Prevention of Falls and Fractures in Old People by Administration of Calcium and Vitamin D. Randomized Clinical Trial (ANVITAD)

The first objective is to determine the efficacy of calcium and vitamin D supplementation at doses of 1200 mg and 800 IU, respectively, to reduce the incidence of falls and fractures in non-institutionalized elderly people.

The second objective is to measure and compare treatment groups (calcium and vitamin D vs placebo) as regards muscle strength and musculoskeletal function, bone mineral density, calcidiol level and treatment safety.

Study Overview

• Status: Unknown
• Conditions: Fall; Fractures
• Intervention / Treatment: Drug: Vitamin D and calcium suplementation

Detailed Description

Background:

There are many studies that associate vitamin D serum levels in older persons with muscle strength, physical performance and risk of fractures and falls. However, current evidence is insufficient to make a general recommendation for administrating calcium and vitamin D to older persons. The objective of this study is to determine the effectiveness of calcium and vitamin D supplementation in improving musculoskeletal function and decreasing the number of falls in person aged over 65 years.

Design:

Phase III, randomized, double blind, placebo-controlled trial to evaluate the efficacy of already marketed drugs in a new indication. It will be performed at Primary Care doctor visits at several Healthcare Centers in different Spanish Health Areas. A total of 704 non-institutionalized subjects aged 65 years or older will be studied (sample size calculated for a statistical power of 80%, alpha error 0.05, annual incidence of falls 30% and expected reduction of 30% to 20% and expected loss to follow up of 20%). The test drug containing 800 IU of vitamin D and 1000 mg of calcium will be administered daily. The control group will receive a placebo. The subjects will be followed up over two years. The primary variable will be the incidence of spontaneous falls. The secondary variables will include: consequences of the falls (fractures, need for hospitalization), change in calcidiol plasma levels and other analytical determinations (transaminases, PTH, calcium/phosphorous, albumin, creatinine, etc.), change in bone mass by densitometry, change in muscle strength in the dominant hand and change in musculoskeletal strength, risk factors for falls, treatment compliance, adverse effects and socio-demographic data.

• Study Type: Interventional
• Enrollment (Anticipated): 704
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Albacete, Spain, 02001
    • Research Unit. Primary Care Head Office of Albacete

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged over 65 years with normal renal function
• Normal transaminase levels
• Normal calcium blood levels
• Not homebound (not immobilized) nor in socio-healthcare institutions.

Exclusion Criteria:

• Need for medical treatment with calcium or vitamin D
• Hypersensitivity to or contraindication for calcium or vitamin D
• Medical treatment that includes calcium or vitamin D
• Physical disability that impedes their collaboration
• Taking thiazide diuretics
• Oral anticoagulants
• Hormone replacement therapy
• Digitalis drugs
• Anticonvulsants or barbiturates

• Having any of the following diseases:

  • Lithiasis
  • Renal impairment (serum creatinine >1.4 mg/dl)
  • Hypo or hyperthyroidism
  • Paget's disease
  • Chronic liver disease
  • Tumors
  • Sarcoidosis
  • Impaired intestinal absorption or chronic alcoholism (>40 g/day).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Calcium and vitamin D; The pharmacological intervention will be the daily administration of chewable tablets containing vitamin D and calcium.	Drug: Vitamin D and calcium suplementation; The pharmacological intervention will be the daily administration of chewable tablets containing 800 IU of vitamin D and 1200 mg of calcium. They will be administered over 2 years during the months of November to April in order to avoid the influence of sunlight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of spontaneous falls.	The primary variable will be the incidence of spontaneous falls according to the FICSIT (Frailty and Injury: Cooperative Study of Intervention Techniques) definition: "Unintentionally coming to rest on the ground, floor, or other lower level. Coming to rest against furniture or a wall was not counted as a fall".	24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consequence of falls.	Bone fractures at any location, need for healthcare, need for hospitalization, bed-ridden.	24 months.
Change in calcidiol [25(OH)D3] plasma levels	Determined by RIA (Vitamin D deficiency is defined as a calcidiol plasma level lower than 10ng/ml).	18 months.
Change in bone mass (bone density or mineral content).	By densitometry (risk of fracture). Osteoporosis will be diagnosed based on a densitometry T-score of less than 2.5 in the vertebral column, according to WHO criteria.	24 months.
Change in muscle strength in the dominant hand.	Determined by dyanometry (with a mean of 3 attempts to obtain a muscle strength measurement).	24 months
Changes in musculoskeletal function.	By the timed up and go test (the elderly person gets up from a chair with arms, walks three meters, turns round, walks back and sits down again). Taking more than 20 seconds indicates a high risk for falls.	24 months
Serious adverse events or any other adverse event.	An adverse event is considered as any untoward medical occurrence in any patient included in the study which does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product.	24 months.

Collaborators and Investigators

• Sponsor: Gerencia de Atención Primaria, Albacete
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Jesús López-Torres, Hidalgo, Research Unit. Primary Care Head Office of Albacete; Study Chair: Ignacio Párraga Martínez, Dr., Research Unit. Primary Care Head Office of Albacete; Study Chair: Beatriz Navarro Bravo, Dr., Research Unit. Primary Care Head Office of Albacete; Study Chair: Fernando Andrés Pretel, Dr., Research Unit. Primary Care Head Office of Albacete

Publications and helpful links

General Publications

• Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005 May 11;293(18):2257-64. doi: 10.1001/jama.293.18.2257.
• Dhesi JK, Bearne LM, Moniz C, Hurley MV, Jackson SH, Swift CG, Allain TJ. Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res. 2002 May;17(5):891-7. doi: 10.1359/jbmr.2002.17.5.891.
• Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003 Feb;18(2):343-51. doi: 10.1359/jbmr.2003.18.2.343.
• Campbell AJ, Robertson MC, Gardner MM, Norton RN, Tilyard MW, Buchner DM. Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women. BMJ. 1997 Oct 25;315(7115):1065-9. doi: 10.1136/bmj.315.7115.1065.
• Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med. 1992 Dec 3;327(23):1637-42. doi: 10.1056/NEJM199212033272305.
• Chapuy MC, Pamphile R, Paris E, Kempf C, Schlichting M, Arnaud S, Garnero P, Meunier PJ. Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int. 2002 Mar;13(3):257-64. doi: 10.1007/s001980200023.
• del Campo MT, Aguado P, Martinez ME. [Vitamin D and bone health: is there a need to review supplementation in osteoporosis risk population?]. Med Clin (Barc). 2005 Dec 3;125(20):788-93. doi: 10.1016/s0025-7753(05)72191-6. Spanish.
• Gillespie WJ, Avenell A, Henry DA, O'Connell DL, Robertson J. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev. 2001;(1):CD000227. doi: 10.1002/14651858.CD000227.
• Janssen HC, Samson MM, Verhaar HJ. Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr. 2002 Apr;75(4):611-5. doi: 10.1093/ajcn/75.4.611.
• Latham NK, Anderson CS, Reid IR. Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc. 2003 Sep;51(9):1219-26. doi: 10.1046/j.1532-5415.2003.51405.x.
• Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med. 1996 Feb 15;124(4):400-6. doi: 10.7326/0003-4819-124-4-199602150-00003.
• NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001 Feb 14;285(6):785-95. doi: 10.1001/jama.285.6.785.
• Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int. 2002 Mar;13(3):187-94. doi: 10.1007/s001980200012.
• Simon J, Leboff M, Wright J, Glowacki J. Fractures in the elderly and vitamin D. J Nutr Health Aging. 2002;6(6):406-12.
• Vallecillo G, Diez A, Carbonell J, Gonzalez Macias J. [Treatment of osteoporosis with calcium and vitamin D. Systematic review]. Med Clin (Barc). 2000 Jun 10;115(2):46-51. doi: 10.1016/s0025-7753(00)71461-8. Spanish.
• van der Wielen RP, Lowik MR, van den Berg H, de Groot LC, Haller J, Moreiras O, van Staveren WA. Serum vitamin D concentrations among elderly people in Europe. Lancet. 1995 Jul 22;346(8969):207-10. doi: 10.1016/s0140-6736(95)91266-5.
• Zamboni M, Zoico E, Tosoni P, Zivelonghi A, Bortolani A, Maggi S, Di Francesco V, Bosello O. Relation between vitamin D, physical performance, and disability in elderly persons. J Gerontol A Biol Sci Med Sci. 2002 Jan;57(1):M7-11. doi: 10.1093/gerona/57.1.m7.
• Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 2003 May;89(5):552-72. doi: 10.1079/BJN2003837.
• Lopez-Torres Hidalgo J; ANVITAD Group. Prevention of falls and fractures in old people by administration of calcium and vitamin D, randomized clinical trial. BMC Public Health. 2011 Dec 9;11:910. doi: 10.1186/1471-2458-11-910.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (ANTICIPATED): November 1, 2011
• Study Completion (ANTICIPATED): April 1, 2012

Study Registration Dates

• First Submitted: October 9, 2011
• First Submitted That Met QC Criteria: October 11, 2011
• First Posted (ESTIMATE): October 14, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 14, 2011
• Last Update Submitted That Met QC Criteria: October 11, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Elderly; Vitamin D; Calcium
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium
• Other Study ID Numbers: 2006001