Condition category
Circulatory System
Date applied
06/09/2006
Date assigned
13/09/2006
Last edited
01/11/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Rainer Rauramaa

ORCID ID

Contact details

Kuopio Research Institute of Exercise Medicine
Haapaniementie 16
Kuopio
FIN-70100
Finland

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

http://www.minedu.fi

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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Additional files

Editorial Notes

01/11/2016: Publication reference added.