Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Dose-Responses to EXercise TRAining: a randomised controlled four year trial on the effects of regular physical exercise and diet on endothelial function, atherosclerosis and cognitive function
Acronym
DR's EXTRA
Study hypothesis
1. Regular aerobic or resistance exercise causing an energy expenditure of 1000 - 1500 kcal/wk (4.2 - 6.3 MJ/wk) reduces the risk of developing metabolic syndrome and type two diabetes, attenuates inflammation, improves endothelial function, diminishes the progression of atherosclerosis, and decreases the risk of cognitive impairment, without additional benefit from higher exercise energy expenditures.
2. Regular aerobic or resistance exercise enhances Nitric Oxide (NO) bioavailability as a consequence of the down-regulation of the modified RiboNucleic Acid (mRNA) of inducible NO Synthase (iNOS), and this effect can be seen as an improved Flow-Mediated Dilatation (FMD) of the brachial artery.
3. Regular aerobic exercise generates muscle specific InterLeukin-6 (IL-6), which induces an anti-inflammatory response by elevating the levels of anti-inflammatory cytokines, reflected by lowering of high sensitivity C-Reactive Protein (hsCRP), and seen as improved FMD of the brachial artery.
4. Regular aerobic or resistance exercise enhance the levels of mitochondrial proteins and further enhance the expression of metabolic genes during acute exercise and thereby improves insulin sensitivity and glucose tolerance.
5. Low saturated fat, high unsaturated fat, high fiber diet, enriched with omega-3 fatty acids, attenuates inflammatory reaction by down-regulating the mRNA of iNOS and Heat Shock Protein HSP72 thereby improving endothelial function, diminishing the progression of atherosclerosis, and decreasing the risk of cognitive impairment.
6. Combined exercise and diet intervention is more powerful for attenuation of inflammatory reaction, improving endothelial function, diminishing the progression of atherosclerosis, and decreasing the risk of cognitive impairment than exercise or diet alone.
Ethics approval
Joint ethics committee of Kuopio University and Kuopio University Hospital
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Endothelial function, atherosclerosis
Intervention
Participants are randomly allocated into:
1. Control group
2. Aerobic exercise
3. Resistance exercise
4. Diet
5. Combined aerobic exercise and diet
6. Combined resistance exercise and diet
Intervention type
Behavioural
Phase
Drug names
Primary outcome measures
Changes in:
1. Atherosclerosis
2. Endothelial function
3. Cognitive function
Secondary outcome measures
Changes in:
1. Inflammatory status
2. Metabolic risk factors
3. Cardiovascular risk factors
Overall trial start date
15/01/2003
Overall trial end date
15/09/2010
Reason abandoned
Eligibility
Participant inclusion criteria
A random population sample of the citizens in Kuopio, aged 55 to 74 years at the time of recruitment
Participant type
Healthy volunteer
Age group
Adult
Gender
Both
Target number of participants
1500
Participant exclusion criteria
Conditions that inhibit safe engagement in prescribed exercise training, malignant diseases and other conditions preventing co-operation, as judged by the research physicians.
Recruitment start date
15/01/2003
Recruitment end date
15/09/2010
Locations
Countries of recruitment
Finland
Trial participating centre
Kuopio Research Institute of Exercise Medicine
Kuopio
FIN-70100
Finland
Sponsor information
Organisation
Ministry of Education (Finland)
Sponsor details
PO Box 29
Helsinki
00023
Finland
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Ministry of Education in Finland (Finland) (refs: 125/722/2003; 116/722/2004; 134/627/2005)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Academy of Finland (Finland) (refs: 102318;104943)
Alternative name(s)
Academy of Finland
Funding Body Type
government organisation
Funding Body Subtype
federal
Location
Finland
Funder name
Kuopio University Hospital (Finland) (refs: 13/2002; 24/2004)
Alternative name(s)
Kuopio University Hospital, KYS
Funding Body Type
private sector organisation
Funding Body Subtype
academic
Location
Finland
Funder name
Diabetes Research Foundation (Finland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
European Union (Belgium) - partner in EXGENESIS consortium (ref: EU 005272)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sydäntutkimussäätiö
Alternative name(s)
Finnish Foundation for Cardiovascular Research
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
Finland
Funder name
Paivikki and Sakari Sohlberg Foundation (Finland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20413523
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/21186108
2012 prediabetic states results in: http://www.ncbi.nlm.nih.gov/pubmed/22415336
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25230681
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/24911019
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25599193
Publication citations
-
Results
Hassinen M, Lakka TA, Hakola L, Savonen K, Komulainen P, Litmanen H, Kiviniemi V, Kouki R, Heikkilá H, Rauramaa R, Cardiorespiratory fitness and metabolic syndrome in older men and women: the dose responses to Exercise Training (DR's EXTRA) study., Diabetes Care, 2010, 33, 7, 1655-1657, doi: 10.2337/dc10-0124.
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Results
Kouki R, Schwab U, Lakka TA, Hassinen M, Savonen K, Komulainen P, Krachler B, Rauramaa R, Diet, fitness and metabolic syndrome--the DR's EXTRA study., Nutr Metab Cardiovasc Dis, 2012, 22, 7, 553-560, doi: 10.1016/j.numecd.2010.10.008.
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Prediabetic states results
Heikkilä HM, Schwab U, Krachler B, Männikkö R, Rauramaa R, Dietary associations with prediabetic states--the DR's EXTRA Study (ISRCTN45977199)., Eur J Clin Nutr, 2012, 66, 7, 819-824, doi: 10.1038/ejcn.2012.23.
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Results
Heikkilä HM, Krachler B, Rauramaa R, Schwab US, Diet, insulin secretion and insulin sensitivity--the Dose-Responses to Exercise Training (DR's EXTRA) Study (ISRCTN45977199), Br J Nutr, 2014, 112, 9, 1530-1541, doi: 10.1017/S0007114514002426.
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Results
Hakola L1, Hassinen M, Komulainen P, Lakka TA, Savonen K, Rauramaa R, Correlates of low physical activity levels in aging men and women: the DR's EXTRA Study (ISRCTN45977199), J Aging Phys Act, 2015 , 23, 2, 247-255, doi: 10.1123/japa.2013-0169.