DO-HEALTH: vitamin D3 - omega3 - home exercise - healthy aging and longevity trial - design of a multinational clinical trial on healthy aging among european seniors

Authors: BISCHOFF-FERRARA, HEIKE - University Hospital Zurich; DE GODOI REZENDE CC - University Of Zurich; RIVAL, SANDRINE - University Of Zurich; VELLAS, BRUNO - Toulouse University Hospital; RIZZOLI, RENE - Geneva University Hospital; KRESSIG, RETO - University Of Basel; KANIS, JOHN - University Of Sheffield; MANSON, JOANN - Harvard University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORAV, ENDEL - Harvard University; DA SILVA, JOSE - University Of Coimbra; BLAUTH, MICHAEL - Innsbruck Medical University; FELSENBERG, DIETER - National Institutes Of Health (NIH); FERRARI, STEPHEN - Ferrari Data Solutions; THEILER, ROBERT - University Of Zurich; EGLI, ANDREAS - University Of Zurich

Submitted to: Contemporary Clinical Trials
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2020
Publication Date: 9/1/2020
Citation: Bischoff-Ferrara, H.A., De Godoi Rezende Costa Caroline, Rival, S., Vellas, B., Rizzoli, R., Kressig, R.W., Kanis, J.A., Manson, J.E., Dawson-Hughes, B., Orav, E.J., Da Silva, J.A., Blauth, M., Felsenberg, D., Ferrari, S.M., Theiler, R., Egli, A. 2020. DO-HEALTH: vitamin D3 - omega3 - home exercise - healthy aging and longevity trial - design of a multinational clinical trial on healthy aging among european seniors. Contemporary Clinical Trials. 100(2021):106124. https://doi.org/10.1016/j.cct.2020.106124.
DOI: https://doi.org/10.1016/j.cct.2020.106124

Interpretive Summary: The number of older adults with age-related chronic diseases is increasing and interventions that are effective, affordable, and well-tolerated in the prevention of chronic conditions are urgently needed. The DO-HEALTH study is a multi-center clinical trial conducted in 2,157 community-dwelling men and women, age 70 and older, at 7 clinical sites in Europe. The trial will test the individual and additive benefit, as well as the cost-effectiveness, of 3 interventions: vitamin D 2,000 IU/day, omega-3 fatty acids 1,000 mg/day and a 30-minute 3 times/week home exercise program. Do-Health will test the effect of these interventions on blood pressure, non-vertebral fractures, muscle performance, cognitive function, and rate of infections. The trial duration is 3 years with in-person contacts with all participants during 4 clinical visits and by quarterly phone calls. Baseline and follow-up blood samples will be collected in all participants to measure changes in vitamin D and poly-unsaturated fatty acid concentrations. This trial may identify interventions that promote healthy aging and longer life expectancy and that can be easily and safely implemented by older community-dwelling adults.

Technical Abstract: DO-HEALTH is a multi-center clinical trial among 2157 community-dwelling European men and women age 70 and older. The 2x2x2 randomized-control factorial design trial tested the individual and additive benefit, as well as the cost-effectiveness, of 3 interventions: vitamin D 2000 IU/day, omega-3 fatty acids 1000 mg/day (EPA + DHA, ratio 1:2), and a 30-minute 3 times/week home exercise (strength versus flexibility). Each treatment tested has shown considerable prior promise from mechanistic studies, small clinical trials, or large cohort studies, in the prevention of common age-related chronic diseases, but definitive data are missing. DO-HEALTH will test these interventions in relation to 6 primary endpoints (systolic and diastolic blood pressure, non-vertebral fractures, Short Physical Performance Battery score, the Montreal Cognitive Assessment, and risk of infections), plus several secondary endpoints explored in ancillary studies (i.e. rate of any falls and injurious falls, joint pain, oral health, quality of life, and incident frailty). As the 3 interventions have distinct mechanisms of action for each of the 6 primary endpoints, a maximum benefit is expected for their additive benefit as a "multi-modal" intervention. The trial duration is 3 years with in-person contacts with all participants at 4 clinical visits and by quarterly phone calls. Baseline and follow-up blood samples were collected in all participants to measure changes in 25-hydroxyvitamin D and poly-unsaturated fatty acid concentrations. Our objective was to test interventions that are expected to promote healthy aging and longer life expectancy and that can be easily and safely implemented by older community-dwelling adults.