Community Research and Development Information Service - CORDIS

FP7

DO-HEALTH Report Summary

Project ID: 278588
Funded under: FP7-HEALTH
Country: Switzerland

Periodic Report Summary 3 - DO-HEALTH (VitaminD3-Omega3-Home Exercise- HeALTHy Ageing and Longevity Trial)

Project Context and Objectives:
The European population is ageing, and the number of adults age 70 and older is predicted to increase from 25% to 40% by 20301-5 as will the number of people with age-related chronic diseases. Thus interventions that prolong the number of years during which seniors are in good health and free from disabilities will have a striking impact on public health.
The goal of DO-HEALTH is to extend healthy life expectancy by delaying physiologic aging at multi-organ sites in European seniors and to reduce healthcare costs via the implementation of effective and broadly applicable disease prevention interventions. This will be achieved within a large multi-centre clinical trial enrolling 2152 community-dwelling men and women aged 70 and older, when chronic diseases increase substantially. The randomized-controlled trial will test the individual and the additive (“multi-modal”) benefit of 2000 IU vitamin D/day, 1 gram of omega-3 fatty acids per day and a simple home exercise program in an efficient factorial trial design. DO-HEALTH will establish evidence for 5 primary endpoints: (1) the risk of incident non-vertebral fractures; (2) the risk of functional decline; (3) the risk of blood pressure increase; (4) the risk of cognitive decline; (5) and the rate of any infection.
Key secondary endpoints include risk of hip fracture, rate of falls, knee pain in symptomatic knee osteoarthritis, glucose tolerance, oral health, gastro-intestinal symptoms, mental health, quality of life, and mortality. The trial duration will be 3 years to establish long-term efficacy and safety data for the 3 interventions. Follow-up will be in-person and in 3-monthly intervals (4 clinical visits and 9 phone follow-up calls). DO-HEALTH will further assess the comparative effectiveness of the interventions by evaluating reasons why or why not seniors adhere to them; and will assess their cost-benefit in a health economic model based on documented health care utilization and observed incidence of chronic disease.

Project Results:
DO-HEALTH has reached 100% recruitment with 2’158 seniors recruited in November 2014!
Despite issues and unexpected delays, e.g., the assessment in period 1 of DO-HEALTH as a drug trial vs a food supplement trial (as originally thought) in all countries except Austria, the differences in regulatory and ethical requirements throughout Europe, the difficulty in recruiting 2152 participants aged 70+, furthermore with a low-trauma fall in the previous 12 months, the suspension of the recruitment in one DO-HEALTH centre for 5 months in period 2, DO-HEALTH has successfully met its recruitment goal, with 2’158 participants recruited in November 2014.

DO-HEALTH trial is progressing very well at all the centres
The follow-up of participants of 1 year was completed overall in November 2015. The follow-up of 2 years is on-going until November 2016, and up to 3 years is on-going until November 2017.
Of the 2’158 seniors age 70 and older recruited between December 2012 and November 2014 into the DO-HEALTH clinical trial, 1’914 seniors keep participating to the trial as of June 2016 (M54). The overall drop-out rate is of 11%.

DO-HEALTH Biobank is created and operational
Fisher Bioservices, one of the largest and most experienced in biobanking services, host the DO-HEALTH biobank. The DO-HEALTH biobank is funded by UZH own resources. Fisher Bioservices organize the shipment of the biological samples from the recruiting centres to the biobank, the sorting of the samples and biobank the samples. The baseline samples collection of all the DO-HEALTH
participants was completed in December 2014. Thermofisher has sorted the aliquots according to their use (analysis, back-up, biobank), and started to ship the aliquots for analyses to three laboratories:
- UZH: organ-specific biomarkers
- DNP: adherence - 25-hydroxyvitamin D and PUFA
- TUD: myostatin and sclerostin biomarkers
From December 2012 to June 2016, DO-HEALTH biobank has handled over 136`102 biosamples.

All the biomarkers in the blood and urine samples from the baseline visit from all DO-HEALTH participants are now available!
DO-HEALTH database contains the full biomarkers dataset for baseline- and 12-month of follow-up, and a partial dataset for 24- and 36-months of follow-up. The full biomarkers datasets for 24- and 36-month of follow-up are expected respectively in June 2017 and March 2018.

First baseline results will be published soon
IDXA data from the IDXA sites of DO-HEALTH and first Tables on questionnaire results from all DO-HEALTH sites have been presented in a preliminary format to partners and collaborators present at the 3-year annual meeting.
Preliminary baseline analyses on vitamin D, EPA, DHA status and on diet patterns were presented at the 4-year annual meeting.

Electronic Data Capture also for the elaborate DO-HEALTH CRFs
The initial plan was to have electronic data entry for the questionnaires and hopefully the CRFs. We had from 2012 to December 2014 a versatile software allowing randomization, supply management, scheduling, trial monitoring, direct data entry of DO-HEALTH questionnaires (EQ5D-3L, PROMIS-HAQ , FFQ, SANGHA, SUNLIGHT, NHSexcerpt, SHARE-FI, KOOS, KNEE, JointMap, McGILL, GDSexcerpt, GOHAI, HOOS, QuickDASH, ROMEIII, MoCA), and data extraction. Plus a 7 day per week support for all software problems at all 7 DO-HEALTH centres, all provided by our partner FDS.
Since January 2015, we also have electronic data capture for the elaborate CRFs (significant work programming and logistics).

Unexpected regulatory issues satisfactorily answered in 2014
Coimbra site was inspected by the Portuguese regulatory authority INFARMED on the 2nd to the 4th of April 2014. At the same visit, INFARMED found that the investigational medical product (IMP) may not comply with the product specification. Given this serious concern, the recruitment at Coimbra had to be suspended from 06/05/2014 to 26/09/2014, however the participants included in the study were allowed to go on with the IMP. INFARMED also informed all other regulatory authorities by sending a Fax “suspected quality defect IMP notification”.
All the concerns raised by INFARMED during their regulatory inspection at UCO were answered. The Coordinating centre and DNP initiated additional actions (e.g., SOPs, analyses) to insure that trial participants are not placed at risk, and that the results of the trial are unaffected by inadequate safety, quality, or efficacy arising from unsatisfactory manufacture.
DO-HEALTH clinical trial is designed and conducted according to GCP, and the IMP is produced as a dietary supplement category 2 in a GMP environment!

Study investigational medical product: its shelf-life is adjusted following the stability program results
DNP is responsible for the DO-HEALTH study medication - vitamin D, omega-3 fatty acids and placebo (sunflower oil) provided in capsules, and DNP agreed to provide the capsules free of charge to DO-HEALTH sites. As the capsules are not commercially-produced capsules, their shelf life had to be estimated and was set to 3 years at the beginning of the trial. The stability program at the DSM Analytical Services laboratory in which the main ingredients of the capsules (e.g., vitamin D / omega-3 fatty acids / high oleic Sunflower oil) are measured under standardized conditions (temperature and humidity) over the course of 4 years has now shown a shorter shelf live for the Capsules. Although the capsules do not constitute any health risk, DNP and the DO-HEALTH Coordination team decided to exchange the capsules earlier than planned. DO-HEALTH sites insure that the capsule batches are exchanged at the set time. The costs are supported by our partner DNP. This is very appreciated by the coordinating team and all other partners in DO-HEALTH!

DO-HEALTH website and dissemination
DO-HEALTH website was created in period 1 http://do-health.eu/wordpress/, and is regularly updated by DO-HEALTH Coordinator.
- “DO-HEALTH in the media” provides the links to videos, articles, newsletters, and the EU flyer for DO-HEALTH.
- “News DO-HEALTH” reports on DO-HEALTH recruitment status, public events, press releases and DO-HEALTH meetings.
- “For partners” includes information specific for DO-HEALTH partners, e.g., recruitment, training, sharing of experiences, GB meetings minutes, newletters.

Annual meetings / Governing Board meetings
Annual meetings take place at at the University of Zurich (Congress Forum Waid City Hospital, Zurich, Switzerland). Four annual meetings were held in periods 1, 2 and 3: http://dohealth.eu/wordpress/annual-partner-meeting-2013/, http://do-health.eu/wordpress/2014-annual-meeting-do-health/, http://do-health.eu/wordpress/2015-3rd-annual-meeting-do-health/, http://do-health.eu/wordpress/4th-annual-meeting/.

Potential Impact:
The DO-HEALTH trial is designed to clarify the role of 3 promising interventions (vitamin D, omega3-fats, home exercise program), both individually and combined as a multi-modal combined intervention in chronic disease prevention at older age.
DO-HEALTH will establish evidence in 5 following primary endpoints: 1) the risk of incident non-vertebral fractures; 2) the risk of functional decline; 3) the risk of blood pressure increase; 4) the risk of cognitive decline; 5) and the rate of any infection.
1) The risk of incident non-vertebral fractures: Fractures are a major problem in seniors and the findings of DO-HEALTH may provide critical evidence in the prevention of fractures at older age. 75% of all fractures occur in the population of 75 years and older and the consequences of fractures are severe, and often result in a second fracture. Recent research suggests that in order to reduce fractures at older age, we need to support bone and muscle health. DO-HEALTH will test 3 promising treatments that have shown promise in this dual concept.
2) The risk of functional decline: Adequate level of mobility and muscle strength is crucial for healthy aging and maintaining quality of life well into the advanced age. There is growing body of evidence that vitamin D and simple physical exercise can significantly improve functional mobility, gait, and balance reducing likelihood of falls in seniors. Effects of omega-3 fatty acids on muscle function are also promising, but long term data are lacking. DO-HEALTH has functionality, mobility and muscle health among its main focus. DO-HEALTH aims to provide evidence that will help seniors live their lives more actively, safer and, ultimately, more enjoyable.
3) The risk of blood pressure increase: Blood pressure rises with age and lowering systolic blood pressurein seniors with hypertension may reduce cardiovascular events and mortality. DO-HEALTH will test 3 promising treatments that have shown promise in the reduction of blood pressure.
4) The risk of cognitive decline: Dementia and Alzheimer disease has a prevalence of over 30% among seniors age 80 years and above. DO-HEALTH will test 3 promising treatments that have shown promise in the reduction of cognitive decline.
5) The rate of any infection: Infections increase with age, and premature deaths from influenza and pneumonia in older adults are rising. DO-HEALTH will test 3 promising treatments that have shown promise in the reduction of infections by immune-stimulation and anti-inflammatory effects.

Other key endpoints include risk of hip fracture, rate of falls, pain in symptomatic knee osteoarthritis, glucose tolerance, gastro-intestinal symptoms, mental and oral health, quality of life, and mortality. Follow-up will be in-person and in 3-monthly intervals (4 clinical visits and 9 phone calls). DO-HEALTH will further assess the comparative effectiveness of the interventions by evaluating reasons why or why not seniors adhere to them, 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 will be the largest aging study to date designed to extend healthy life expectancy by delaying physiologic aging at multi-organ sites.

Project Coordinator:
Prof. H. A. Bischoff-Ferrari, MD, DrPH- UZH (University of Zurich), Switzerland
E-mail: Heike.Bischoff@usz.ch

List of Websites:
www.do-health.eu

Related information

Reported by

UNIVERSITAET ZUERICH
Switzerland

Subjects

Life Sciences
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