Project Description

Full title: VitaminD3-Omega3-Home Exercise- HeALTHy Ageing and Longevity Trial

Background

The European population is aging rapidly which poses a challenge on the individual, the European societies, and health care systems. Among the most promising public health interventions that may extend healthy life expectancy at older age are vitamin D, marine omega-3 fatty acids and physical exercise. However, their individual and combined effects have yet to be confirmed in a clinical trial.

Main aims of DO-HEALTH

  • To support healthy aging in European seniors
  • To reduce healthcare costs via the implementation of effective and broadly applicable disease prevention interventions

Specific aims of DO-HEALTH

  • To establish whether vitamin D, omega-3 fatty acids, and a simple home exercise program will prevent disease at older age
  • To assess the cost-benefit of the interventions

Methods

To achieve these aims, DO-HEALTH will enroll 2152 community-dwelling men and women who are 70 years and older, an age when chronic diseases increase substantially. The DO-HEALTH seniors will be recruited from 7 European cities (Zurich, Basel, Geneva, Toulouse, Berlin, Innsbruck and Coimbra) and will be randomized in a 2x2x2 factorial design trial to a simple home exercise program and/or vitamin D, and/or omega-3 fatty acids, over a 3 year period.   This will allow to test the individual and the combined benefit of the interventions in the prevention of 5 primary endpoints: the risk of incident non-vertebral fractures; the risk of functional decline; the risk of blood pressure increase; the risk of cognitive decline; and the rate of any infection. Key secondary endpoints include risk of hip fracture, rate of falls, pain in symptomatic knee osteoarthritis, gastro-intestinal symptoms, mental and oral health, quality of life, and life-expectancy.

All clinical endpoints will be supported by a large DO-HEALTH biomarker study to evaluate the effect of the interventions at the cellular level of multi-organ function. DO-HEALTH will further evaluate reasons why or why not seniors adhere to the 3 interventions, and will assess their cost-benefit in a health economic model based on documented health care utilization and observed incidence of chronic disease.

DO-HEALTH seniors will be followed for 3 years, in-person, and in 3-monthly intervals (4 clinical visits and 9 phone calls) at the 7 recruitment centers.

Study population

DO-HEALTH will enroll seniors age 70 years and older. To represent the largest part of the senior population, DO-HEALTH will recruit community-dwelling seniors. However, to represent also the pre-frail population at risk of institutionalization, 50% of seniors will be enrolled based on a fall with or without a fracture in the year before DO-HEALTH enrolment.

Study Design

This is a randomized, double-blind, placebo-controlled, 2×2×2 factorial design clinical trial. The trial will be performed at 7 recruitment centers located in 5 countries: Switzerland (University of Zurich, Basel University Hospital, Geneva University Hospital), France (University of Toulouse Hospital Centre), Germany (Charité Berlin), Portugal (University of Coimbra), and Austria (Innsbruck Medical University).

Randomization

Stratified Block Randomization will be performed by the DO-HEALTH randomization software. Labeling of study intervention will be performed by a central randomization centre in Switzerland.

Stratification variables: recruitment centre (7 centers), fall during previous 12 months (yes/no), gender, and age (70 – 84 and 85+). Even balance among those who fell or did not fall during the last year will be enforced at each of the 7 recruitment centers. Gender and age distribution will be monitored within each recruitment centre with the DO-HEALTH randomization software. If gross imbalance (less than 30% of participants in a stratum) is detected within a centre, recruitment strategies for the centre will be adapted to boost recruitment of participants of underrepresented category