E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
healthy ageing, functional decline |
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E.1.1.1 | Medical condition in easily understood language |
healthy ageing, functional decline |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Broad Goals
The DO-HEALTH trial is designed to establish evidence for the role of
vitamin D, omega-3 fatty acids, and a simple exercise program, both
individually and as a combined intervention, in chronic disease
prevention at older age.
Objectives
Main Objectives:
• To improve healthy ageing in European seniors
• To reduce healthcare costs via the implementation of effective and broadly applicable disease prevention interventions |
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E.2.2 | Secondary objectives of the trial |
Scientific Objectives:
• To test whether 2000 IU vitamin D reduces risk of chronic disease in seniors compared to placebo
• To test whether 1 g of marine omega-3 fatty acids (EPA+DHA) reduces the risk of chronic disease in seniors compared to placebo
• To test whether a simple home exercise program reduces the risk of chronic disease in seniors compared to control (sham exercise performed 30 minutes 3 times a week)
• To test whether there is an additive value of the 3 interventions combined as a multi-modal intervention in the reduction of chronic disease in seniors
• To assess the comparative effectiveness of the interventions and to test whether and to what degree adherence modulates the effect of the 3 interventions on risk reduction of chronic disease in seniors
• To assess the cost-benefit of the 3 interventions individually and in combination as a multi-modal intervention based on an objective health economic mode
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Fracture Healing study, 02.07.2012, version 1.
Fracture healing is a novel endpoint and DO-HEALTH will be one of the first RCTs to assess fracture healing at 3 levels in individuals with incident major osteoporotic fractures at the arm (shoulder, humerus, forearm) and leg (hip, femur, ankle): (a) primary fracture healing endpoint: clinical fracture healing with 3 additional phone calls at 6, 12, 18 weeks after the fracture assessing the PROMIS-HAQ (b) secondary fracture healing endpoint: observed functional fracture healing measured with the Short Physical Performance Test Battery and grip strength at regular 12, 24, 36 month visits (c) exploratory fracture healing endpoint: radiological fracture healing with independent assessment of early (6-8 weeks) and late (12 to 14 weeks) consolidation assessment based on standard x-rays. |
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E.3 | Principal inclusion criteria |
- Mini Mental State Examination Score of at least 24
- Living in the community
- Sufficiently mobile to come to the study centre, to walk 10 meters with or without walking aid and to get in and out of a chair without help
- Able to swallow study medication
- Able and willing to participate, sign informed consent (including
consent to analyze all samples until withdrawal) and cooperate with
study procedures |
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E.4 | Principal exclusion criteria |
(1) Consumption of more than 1000 IU vitamin D/day in the 6 month prior to enrolment, and/or a bolus of 300'000 IU vitamin D or more in the 12 month prior to enrolment, 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
(2) Unwillingness to limit calcium supplement dose to 500 mg per day for the duration of the trial
(3) Taking omega-3 fat supplements and unwilling to forgo their use for the duration of the trial
(4) 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
(5) 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)
(6) 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
(7) Severe renal impairment (creatinine clearance ≤ 15 ml/min) or
dialysis, hypercalcaemia (> 2.6 mmol/l)
(8) Hemiplegia or other severe gait impairment
(9) History of hypo- or primary hyper-parathyroidism
(10) Severe liver disease
(11) History of granulomatous diseases (i.e. tubercolosis, sarcoidosis)
(12) Major visual or hearing impairment or other serious illness that would preclude participation
(13) Living with a partner who is enrolled in DO-HEALTH (we exclude couples)
(14) Living in assisted living situations or a nursing home
(15) Temporary exclusion: acute fracture in the last 6 weeks
(16) Epilepsy and/or use of anti-epileptic drugs
(17) Individuals who fell more than 3 times in the last month
(18) Osteodystrophia deformans (M. Paget, Paget's disease) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints:
(1) Bone: Incident non-vertebral fractures over 36 months (confirmed by X-ray or medical reports)
(2) Muscle: Functional decline (assessed by Short Physical
Performance Test Battery)
(3) Cardiovascular: Systolic and diastolic blood pressure change
(4) Brain: Cognitive decline (assessed by Mini Mental State
Examination)
(5) Immunity: rate of any infection |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The evaluation of the primary endpoints will perform at baseline and then at the annual visits including the final visit after three years. The numbers of infection will additional collect during the telephone calls every three months. |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints:
To support the primary endpoints and extend to other organ systems:
(1) Bone: incidence of hip fractures, incidence of new vertebral
fractures (vertebral morphometry obtained with DEXA measurements), incidence of total fractures – (DEXA measurements), risk of bone mineral density decrease in the spine and hip (assessed by DEXA measurements)
(2) Muscle: rate of falling (rate of any low trauma fall, rate of
injurious falls, number of persons who fell), reaction time and grip
strength, incidence of muscle mass decrease at the upper and lower extremities (DEXA measurements), musculoskeletal pain, dual tasking 10 meter gait speed
(3) Cardiovascular: risk of incident hypertension
(4) Brain: mental health decline, incident depression, dual tasking
gait variability
(5) Immunity: rate of any upper respiratory infection, incident flu-like illness, incident severe infections that lead to hospital admission
(6) Bone/Cartilage: Arthritis: primary outcome for osteoarthritis will be severity of knee pain (KOOS) in those with symptomatic knee osteoarthritis, secondary outcomes for osteoarthritis will be: rate of knee buckling, NSAID use because of knee pain; number of joints with pain
(7) Dental: decline in oral health, tooth loss
(8) Gastro-intestinal: gastro-intestinal symptoms based on Rome III questionnaire
(9) Glucose-metabolic: fasting glucose and insulin levels, QUICKI and HOMA index, body composition and increase in body fat in the trunk and extremities by DEXA
(10) Kidney: decline in kidney function – by blood creatinine levels
and estimated GFR
(11) Global Health: quality of life, incident frailty, incident disability
regarding activities of daily living, incident nursing home admissions, rate of acute hospital admissions, mortality
Exploratory Endpoints:
To support the primary endpoints, but have limited statistical power:
(1) Bone: Incident repeat fractures (any non-vertebral in all
participants, vertebral fractures and total fractures among participants with IDXA measurements). Ancillary fracture healing study in all seniors with an incident major osteoporotic fractures at the arm (shoulder, humerus, forearm) and leg (hip, femur, ankle): (a) primary fracture healing endpoint: clinical
fracture healing (HAQ-Promis questionnaire), (b) secondary fracture healing endpoint: observed functional fracture healing measured with the Short Physical Performance Test Battery and grip strength, (c) exploratory fracture healing endpoint: radiological fracture healing with independent assessment of early and late consolidation assessment based on standard x-rays.
(2) Muscle: incident sarcopenia, incident frailty, decline in physical
activity
(3) Cardiovascular: major cardiovascular events as a composite
endpoint (any event: myocardial infarction, stroke, vascularization
procedures of CABG and PCI, incident congestive heart disease,
cardiovascular mortality); individual endpoints: myocardial infarction, stroke, incident congestive heart disease, and cardiovascular mortality
(4) Brain: incident dementia
(5) Immunity: incident cancer (any cancer, gastro-intestinal, breast
cancer in women, prostate cancer in men); rate of implant infections
after total hip or knee replacement (due to fracture or osteoarthritis);
rate of gastro-intestinal infections
(6) Bone/Cartilage-Arthritis: incident symptomatic knee
osteoarthritis; incident symptomatic hip osteoarthritis, incident
symptomatic hand osteoarthritis; composite endpoint: incident
symptomatic knee, hip or hand osteoarthritis; severity of hip pain in
those with prevalent symptomatic hip osteoarthritis, severity of hand
pain in those with prevalent symptomatic hand osteoarthritis
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
during the clinical visits at Baseline and after 12, 24, 36 months, some of the secondary endspoints (falls, fracture, infections) are evaluate during the telephone call every three months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 8 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |