DO-HEALTH / Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial

NCT01745263 | Completed Phase 3 DMC

• 2 other identifiers: KEK-ZH-2012-0249DO-HEALTH
• Study Type: interventional
• Target: 2,157
• Locations: 5 countries
• Sites: 7

Brief Summary

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. The broad aim of DO-HEALTH is to prolong healthy life expectancy in European seniors. The specific aim is to establish whether vitamin D, omega-3 fatty acids, and a simple home exercise program will prevent disease at older age. 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: incident non-vertebral fractures; functional decline; systolic and diastolic blood pressure change; cognitive decline; and the rate of any infection. Key secondary endpoints include incidence of hip fractures, rate of falls, severity of pain in symptomatic knee osteoarthritis, gastro-intestinal symptoms, mental and oral health, quality of life, and mortality. 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. website DO-HEALTH: http://do-health.eu/wordpress/

Conditions

Improve Healthy Ageing in Seniors; Prevent Disease at Older Age

Outcome Measures

Primary Outcomes (5)

• Bone: Incident non-vertebral fractures over 36 months

  Confirmed by medical and/or x-ray reports

  over 36 months

• Muscle: Functional decline (lower extremity function)

  Measured with the SPPB (short physical performance test battery)

  Baseline, 12, 24 and 36 months

• Cardio-vascular: Systolic and diastolic blood pressure change

  Standardized blood pressure assessment in sitting position

  Baseline, 12, 24 and 36 months

• Brain: Cognitive decline

  Montreal Cognitive Assessment (MoCA)

  Baseline, 12, 24 and 36 months

• Immunity: Rate of any infections

  3-monthly incident infection protocol

  Baseline, and every 3 months up to 36 months

Secondary Outcomes (28)

• Bone: Incident hip fractures

  36 months

• Bone: Incident total fractures

  36 months

• Bone: Incident vertebral fractures

  36 months

• Bone: Bone mineral density decrease at the lumbar spine and hip

  Baseline, 12, 24, and 36 months

• Muscle: Rate of falls

  Assessed every 3 months over 36 months

Other Outcomes (9)

• Biomarker endpoints

  Baseline, 12, 24, and 36 months

• Bone: Incident repeat fractures

  36 months

• BONE: Functional recovery after long bone fracture

  36 months

Study Arms (8)

VitD-Omega3-StrengthExercise

ACTIVE COMPARATOR

Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)

Drug: Vitamin D3; Drug: Omega 3 fatty acids; Procedure: Strength Home Exercise

VitD-Omega3-FlexibilityExercise

ACTIVE COMPARATOR

Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)

Drug: Vitamin D3; Drug: Omega 3 fatty acids; Procedure: Flexibility Home Exercise

Placebo-Omega3-StrengthExercise

ACTIVE COMPARATOR

Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)

Drug: Omega 3 fatty acids; Procedure: Strength Home Exercise

Placebo-Omega3-FlexibilityExercise

ACTIVE COMPARATOR

Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)

Drug: Omega 3 fatty acids; Procedure: Flexibility Home Exercise

VitD-Placebo-StrengthExercise

ACTIVE COMPARATOR

Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3\*30 minutes/week)

Drug: Vitamin D3; Procedure: Strength Home Exercise

VitD-Placebo-FlexiblityExercise

ACTIVE COMPARATOR

Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3\*30 minutes/week)

Drug: Vitamin D3; Procedure: Flexibility Home Exercise

Placebo-Placebo-StrengthExercise

ACTIVE COMPARATOR

Placebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3\*30 minutes/week)

Procedure: Strength Home Exercise

Placebo-Placebo-FlexibilityExercise

SHAM COMPARATOR

Placebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3\*30 minutes/week)

Procedure: Flexibility Home Exercise

Interventions

Vitamin D3 DRUG

2000 IU/d

Also known as: Cholecalciferol

VitD-Omega3-FlexibilityExercise; VitD-Omega3-StrengthExercise; VitD-Placebo-FlexiblityExercise; VitD-Placebo-StrengthExercise

Omega 3 fatty acids DRUG

Ratio EPA:DHA = 1:2 1 g/d

Also known as: Eicosapentaenoic acid AND Docosahexaenoic acid

Placebo-Omega3-FlexibilityExercise; Placebo-Omega3-StrengthExercise; VitD-Omega3-FlexibilityExercise; VitD-Omega3-StrengthExercise

Strength Home Exercise PROCEDURE

Placebo-Omega3-StrengthExercise; Placebo-Placebo-StrengthExercise; VitD-Omega3-StrengthExercise; VitD-Placebo-StrengthExercise

Flexibility Home Exercise PROCEDURE

Placebo-Omega3-FlexibilityExercise; Placebo-Placebo-FlexibilityExercise; VitD-Omega3-FlexibilityExercise; VitD-Placebo-FlexiblityExercise

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 70 years or older
• Mini Mental State Examination Score of at least 24
• Living in the community
• Sufficiently mobile to come to the study centre
• Able to walk 10 meters with or without a walking aid and able to get in and out of a chair without help
• Able to swallow study capsules
• Able and willing to participate, sign informed consent (including consent to analyze all samples until drop-out or withdrawal) and cooperate with study procedures

You may not qualify if:

• Consumption of more than 1000 IU vitamin D/day in the 36 months prior to enrollment, or a bolus of 300'000 IU or more in the last 12 month prior to enrollment, and/ or unwillingness to limit vitamin D intake to the current standard of 800 IU/day of vitamin D during the course of the trial. Provision 1: an individual who consumed an average vitamin D dose between 1000 and 2000 IU vitamin D/day in the 3 months prior to enrollment, may be enrolled after a 3-month wash-out period where the maximum daily intake is limited to 800 IU vitamin D. Provision 2: an individual who consumed an average vitamin D dose higher than 2000 IU/day in the 3 months prior to enrollment, may be enrolled after a 6-month wash-out period where the maximum daily intake is limited to 800 IU vitamin D.
• Unwillingness to limit calcium supplement dose to 500 mg per day for the duration of the trial
• Taking omega-3 fat supplements in the 3 month prior to enrolment and unwilling to forgo their use for the duration of the trial
• Use of any active vitamin D metabolite (i.e. Rocaltrol, alphacalcidiol), PTH treatment (i.e. Teriparatide), or Calcitonin at baseline and unwillingness to forego these treatments during the course of the trial
• Current or recent (previous 4 months) participation in another clinical trial, or plans of such participation in the next 3 years (corresponding to DO-HEALTH length)
• Presence of the following diagnosed health conditions in the last 5 years: history of cancer (except non-melanoma skin cancer); myocardial infarction, stroke, transient ischemic attack, angina pectoris, or coronary artery intervention
• Severe renal impairment (creatinine clearance = 15 ml/min) or dialysis, hypercalcaemia (\> 2.6 mmol/l)
• Hemiplegia or other severe gait impairment
• History of hypo- or primary hyperparathyroidism
• Severe liver disease
• History of granulomatous diseases (i.e. tuberculosis, sarcoidosis)
• Major visual or hearing impairment or other serious illness that would preclude participation
• Living with a partner who is enrolled in DO-HEALTH (i.e. only one person per household can be enrolled)
• Living in assisted living situations or a nursing home
• Epilepsy and/or use of anti-epileptic drugs

Sponsors & Collaborators

• University of Zurich: lead
• Recruitment Partners: collaborator
• University of Geneva, Switzerland: collaborator
• University of Basel: collaborator
• University Hospital, Toulouse, France (Prof. Bruno Vellas, MD): collaborator
• Charite University, Berlin, Germany: collaborator
• Medical University Innsbruck: collaborator
• University of Coimbra, Portugal (Prof. José daSilva, MD): collaborator
• Other University Partners: collaborator
• University of Sheffield: collaborator
• University of Manchester, UK (Prof. David Felson, MD MPH): collaborator
• Max Rubner University, Germany (Prof. Bernhard Watzl, PhD): collaborator
• Technische Universität Dresden: collaborator
• Impact Partner: collaborator
• International Osteoporosis Foundation (IOF; Prof. John Kanis, MD): collaborator
• SME Partners: collaborator
• Ferrari Data Solution: collaborator
• Gut Pictures, Switzerland (Benno Gut; animated exercise video): collaborator
• NOVAMEN, France (Sandrine Rival; logistic management partner): collaborator
• Pharmalys, UK (Marieme Ba; monitoring partner): collaborator
• Industry Partners: collaborator
• DSM Nutritional Products (Dr. Elisabeth Stöcklin PhD, Dr. Manfred Eggersdorfer PhD): collaborator
• Nestlé (Michaela Höhne PhD, Irène Corthesy PhD): collaborator
• Roche Diagnostics GmbH: collaborator
• European Commission: collaborator
• Further collaborators and advisors at website do-health.eu: collaborator

Study Sites (7)

University of Innsbruck

Innsbruck, Austria

Location

University of Toulouse - Centre de Recherche - Gérontopôle Hôpital La Grave

Toulouse, France

Location

Charité Berlin

Berlin, Germany

Location

University of Coimbra - Clínica Universitária de Reumatologia

Coimbra, Portugal

Location

Centre on Aging and Mobility, University of Zurich and City Hospital Waid

Zurich, Canton of Zurich, 8091, Switzerland

Location

Basel University

Basel, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, Switzerland

Location

Related Publications (9)

• Wieczorek M, Funk J, Mattle M, Gangler S, Egli A, Kressig RW, Manz MG, Bischoff-Ferrari HA; DO-HEALTH Research group. Association between hemoglobin levels and mild cognitive impairment in generally healthy European community-dwelling older adults: a 3-year prospective analysis of the DO-HEALTH trial. Am J Clin Nutr. 2025 Nov 13:101114. doi: 10.1016/j.ajcnut.2025.11.005. Online ahead of print.

  PMID: 41241003 DERIVED

• Kistler-Fischbacher M, Gohar G, de Godoi Rezende Costa Molino C, Geiling K, Meyer-Heim T, Kressig RW, Orav EJ, Vellas B, Guyonnet S, da Sliva JAP, Rizzoli R, Armbrecht G, Steinhagen-Thiessen E, Egli A, Bischoff-Ferrari HA. Cognitive function in generally healthy adults age 70 years and older in the 5-country DO-HEALTH study: MMSE and MoCA scores by sex, education and country. Aging Clin Exp Res. 2025 Mar 17;37(1):88. doi: 10.1007/s40520-025-02946-4.

  PMID: 40095212 DERIVED

• de Godoi Rezende Costa Molino C, Forster CK, Wieczorek M, Orav EJ, Kressig RW, Vellas B, Egli A, Freystaetter G, Bischoff-Ferrari HA; DO-HEALTH Research Group. Association of fall risk-increasing drugs with falls in generally healthy older adults: a 3-year prospective observational study of the DO-HEALTH trial. BMC Geriatr. 2024 Nov 29;24(1):980. doi: 10.1186/s12877-024-05557-2.

  PMID: 39614147 DERIVED

• Gaengler S, Sadlon A, De Godoi Rezende Costa Molino C, Willett WC, Manson JE, Vellas B, Steinhagen-Thiessen E, Von Eckardstein A, Ruschitzka F, Rizzoli R, da Silva JAP, Kressig RW, Kanis J, Orav EJ, Egli A, Bischoff-Ferrari HA. Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial. J Nutr Health Aging. 2024 Feb;28(2):100037. doi: 10.1016/j.jnha.2024.100037. Epub 2024 Jan 9.

  PMID: 38199870 DERIVED

• Gagesch M, Wieczorek M, Abderhalden LA, Lang W, Freystaetter G, Armbrecht G, Kressig RW, Vellas B, Rizzoli R, Blauth M, Orav EJ, Egli A, Bischoff-Ferrari HA. Grip strength cut-points from the Swiss DO-HEALTH population. Eur Rev Aging Phys Act. 2023 Aug 5;20(1):13. doi: 10.1186/s11556-023-00323-6.

  PMID: 37543639 DERIVED

• Bischoff-Ferrari HA, Willett WC, Manson JE, Dawson-Hughes B, Manz MG, Theiler R, Braendle K, Vellas B, Rizzoli R, Kressig RW, Staehelin HB, Da Silva JAP, Armbrecht G, Egli A, Kanis JA, Orav EJ, Gaengler S. Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial. Front Aging. 2022 Apr 25;3:852643. doi: 10.3389/fragi.2022.852643. eCollection 2022.

  PMID: 35821820 DERIVED

• de Godoi Rezende Costa Molino C, Chocano-Bedoya PO, Sadlon A, Theiler R, Orav JE, Vellas B, Rizzoli R, Kressig RW, Kanis JA, Guyonnet S, Lang W, Egli A, Bischoff-Ferrari HA; DO-HEALTH Research Group. Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries: a cross-sectional study of DO-HEALTH. BMJ Open. 2022 Apr 29;12(4):e051881. doi: 10.1136/bmjopen-2021-051881.

  PMID: 35487733 DERIVED

• Schietzel S, Chocano-Bedoya PO, Sadlon A, Gagesch M, Willett WC, Orav EJ, Kressig RW, Vellas B, Rizzoli R, da Silva JAP, Blauth M, Kanis JA, Egli A, Bischoff-Ferrari HA. Prevalence of healthy aging among community dwelling adults age 70 and older from five European countries. BMC Geriatr. 2022 Mar 2;22(1):174. doi: 10.1186/s12877-022-02755-8.

  PMID: 35236290 DERIVED

• Bischoff-Ferrari HA, Vellas B, Rizzoli R, Kressig RW, da Silva JAP, Blauth M, Felson DT, McCloskey EV, Watzl B, Hofbauer LC, Felsenberg D, Willett WC, Dawson-Hughes B, Manson JE, Siebert U, Theiler R, Staehelin HB, de Godoi Rezende Costa Molino C, Chocano-Bedoya PO, Abderhalden LA, Egli A, Kanis JA, Orav EJ; DO-HEALTH Research Group. Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial. JAMA. 2020 Nov 10;324(18):1855-1868. doi: 10.1001/jama.2020.16909.

  PMID: 33170239 DERIVED

Related Links

• European Commission project link for DO-HEALTH
• Website DO-HEALTH Consortium

MeSH Terms

Interventions

Cholecalciferol; Fatty Acids, Omega-3; Eicosapentaenoic Acid; Docosahexaenoic Acids

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Dietary Fats, Unsaturated; Dietary Fats; Fats; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Eicosanoids

Study Officials

• Heike Bischoff Ferrari, Prof MD

  "Centre on Aging and Mobility" University of Zurich, University Hospital Zurich and City Hospital Waid.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Centre on Aging and Mobility

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: December 10, 2012
• Study Start: December 20, 2012
• Primary Completion: November 17, 2017
• Study Completion: January 19, 2018
• Last Updated: August 9, 2018

Record last verified: 2018-08

Locations

AU (1); FR (1); CH (3); DE (1); PT (1)