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

Fall Clinical Trial

— ANVITAD  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01452243
• Other study ID #: 2006001
• Status: Active, not recruiting
• Phase: Phase 3
• First received: October 9, 2011
• Last updated: October 11, 2011
• Start date: November 2008
• Est. completion date: April 2012

Study information

• Verified date: October 2011
• Source: Gerencia de Atención Primaria, Albacete
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 704
• Est. completion date: April 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Fall
• Fractures
• Fractures, Bone

Intervention

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.

Locations

Country	Name	City	State
Spain	Research Unit. Primary Care Head Office of Albacete	Albacete

Sponsors (2)

Lead Sponsor	Collaborator
Gerencia de Atención Primaria, Albacete	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & Publications (18)

Bischoff HA, Stähelin 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. — View Citation

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. Review. — View Citation

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. — View Citation

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 the elderly women. N Engl J Med. 1992 Dec 3;327(23):1637-42. — View Citation

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. — View Citation

del Campo MT, Aguado P, Martínez 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. Review. Spanish. — View Citation

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. — View Citation

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. Review. Update in: Cochrane Database Syst Rev. 2005;(3):CD000227. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001 Feb 14;285(6):785-95. Review. — View Citation

Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int. 2002 Mar;13(3):187-94. Review. — View Citation

Simon J, Leboff M, Wright J, Glowacki J. Fractures in the elderly and vitamin D. J Nutr Health Aging. 2002;6(6):406-12. Review. — View Citation

Vallecillo G, Díez A, Carbonell J, González Macías J. [Treatment of osteoporosis with calcium and vitamin D. Systematic review]. Med Clin (Barc). 2000 Jun 10;115(2):46-51. Review. Spanish. — View Citation

van der Wielen RP, Löwik 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. — View Citation

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. — View Citation

Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 2003 May;89(5):552-72. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	Consequence of falls.	Bone fractures at any location, need for healthcare, need for hospitalization, bed-ridden.	24 months.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	No
Secondary	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	No
Secondary	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.	Yes