HealthyTirolGESUNDNCT05678426
TirolGESUND: Baseline-controlled Comparison of the Effects of Fasting Dietary Intervention or Smoking Cessation Combined With Exercise in Healthy Female Tyrolean Volunteers Aged 30-60 on Epigenetic and Multi-omic Biomarkers of Health, Ageing, and Disease
A study testing Smoking cessation, Intermittent fasting and Intermittent fasting with ketogenic supplement in people with Healthy and Healthy Lifestyle, run by Universitaet Innsbruck at 1 site in Austria.
Trial summary
The goal of this clinical study is to learn about disease-risk and age-associated changes in DNA methylation patterns associated with disease risk or age in healthy women aged 30-60 in response to health-promoting lifestyle intervention (intermittent fasting or smoking cessation). Read more about this study
- Who is it for?
- Ages 30 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy, Healthy Lifestyle, Smoking Cessation
- What is being tested?
- Smoking cessation, Intermittent fasting and Intermittent fasting with ketogenic supplement
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 1 siteAustria
- Study dates
- 21 Apr 2021to 4 Sep 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women aged 30 to 60
- Motivated to change their lifestyle
- Smoking cessation intervention:
- 3a. Smoking cessation: ≥10 cigarettes per day for at least the last five years
- Dietary intervention:
- 3b Dietary intervention: BMI between 25 and 35
- NB [Nota Bene], should 3a and 3b apply, participant will be allocated to the smoking cessation intervention.
Who cannot join
- Relevant underlying conditions:
- Current or previous malignant tumour or cancer
- Current or previous significant cardiovascular disorder [participants with elevated blood pressure are allowed to participate as long as it is well controlled under their current medication]
- Current or previous metabolic disorder (e.g., diabetes type I or II) [in the dietary intervention arm, participants with current hypothyroidism/Morbus Hashimoto will be excluded as the switch to intermittent fasting may require a adjustment of their medication]
- Current or previous psychiatric disorder (e.g., eating disorder, depression)
- Current pregnancy or lactation period
Show all 9Show fewer
- Total hysterectomy
- Known current or previous premalignant lesion of the cervix uteri (CIN2/3)
- Concurrent participation in another interventional trial
Trial locations and contacts
1 site in 1 country.
Austria1 site
European Translational Oncology Prevention and Screening Institute
Hall in Tirol, Tyrol, 6060
About this study
Official title: TirolGESUND: General Exercise, Smoking Undone, and Nutrition Diet
The goal of this clinical study is to learn about disease-risk and age-associated changes in DNA methylation patterns associated with disease risk or age in healthy women aged 30-60 in response to health-promoting lifestyle intervention (intermittent fasting or smoking cessation). The main questions the study aims to answer are:
- Are the scores of DNA methylation in epigenetic signatures associated with age, women's cancer risk, or risk exposure reduced after 6 months of lifestyle intervention compared to baseline?
- What are the dynamics of DNA methylation changes during or following intervention, and do differences in changes between different sample types exist?
- Which other biomarkers of health and disease, including metabolic changes, microbiome, clinical, mental, or inflammatory parameters, are altered following intervention?
Read more
The investigators also aim to explore whether DNA methylation changes are associated with changes in other biomarkers mentioned above.
Participants will be allocated to intermittent fasting or smoking cessation based on inclusion criteria. Intermittent fasting encompasses a 16:8 intermittent fasting schedule. Food intake is limited to an 8 h window per day with fasting for the remaining 16 h. Within the intermittent fasting study, participants are randomised to receive a ketogenic supplement (medium-chain triglyceride fibre) or not. Participants in the smoking cessation study will be guided to stop smoking. All participants will receive 1:1 personal coaching throughout the study, and will be provided with an optional exercise programme. All participants will also receive nutritional advice from a professional dietician throughout the study. Participants are invited to donate samples every 2 months for 6 months.
Researchers will compare signatures at the start and after 6 months of intervention. Within the intermittent fasting group, researchers will compare effects in individuals that received the ketogenic supplement to those that did not.
Read the detailed description
Background and study aims: A recent study reported that a majority of malignancies may be caused modifiable risk factors and could therefore be prevented. Smoking and diet are known risk factors for cancer but also other disorders such as cardiovascular or metabolic disorders and neurodegeneration, and may promote premature cellular ageing. The investigators and others have recently described epigenetic signatures for risk of being diagnosed, or developing future, women's cancers, as well as signatures reflecting cellular ageing and exposure to risk factors such as smoking. Utilization of DNA methylation biomarkers as surrogate endpoints indicative of current and/or future disease risk could improve future efforts in preventive medicine, both by providing information on disease risk and biofeedback. Few longitudinal studies have so far investigated the effects of lifestyle changes on DNA methylation and other biomarkers of health and disease.
TirolGESUND investigates the effect of two lifestyle interventions, smoking cessation or intermittent fasting (both with additional optional exercise), over 6 months for the promotion of health and reduction of disease risk, focusing on women's cancers.
Hypothesis: Intermittent fasting or smoking cessation for a duration of 6 months result in a modulation of scores of disease risk- and age-associated DNA methylation biomarker signatures in cervical samples, indicating a reduction of disease risk, exposure, or cellular ageing.
Study design: TirolGESUND is a baseline-controlled intervention study with two parallel arms, smoking cessation and intermittent fasting. Participants are allocated to the study arm based on eligibility criteria. Within the intermittent fasting arm, participants are randomised to receive a ketogenic supplement or not. Ketosis has been suggested to elicit beneficial metabolic alterations and could therefore further enhance beneficial effects in the dietary intervention.
Endpoints: The primary endpoint are score changes in epigenetic biomarkers of cellular ageing and disease risk, primarily recently published Women's cancer risk identification (WID) indices.
In secondary and subsidiary outcomes, the study will explore temporal and spatial dynamics of DNA methylation alterations in response to lifestyle interventions, comparing different surrogate samples (blood, buccal, cervical).
The study also investigates the impact of lifestyle intervention on other biomarkers of health and disease as a pilot study for future behavioural studies in the space of disease prevention and ageing research.
Intervention: Participants will be allocated to intermittent fasting or smoking cessation based on inclusion criteria. Intermittent fasting encompasses a 16:8 intermittent fasting schedule. Food intake is limited to an 8 h window per day with fasting for the remaining 16 h. Within the intermittent fasting study, participants are randomised to receive a ketogenic supplement (medium-chain triglyceride fibre) or not. Participants in the smoking cessation study will be guided to stop smoking. All participants will receive 1:1 personal coaching throughout the study, and will be provided with an optional exercise programme. All participants will also receive nutritional advice from a professional dietician throughout the study.
The duration of the study including intervention is 6 months for each participant. Participants are invited to return for optional sample collection visits at 12 and 18 months.
Visits and examinations: The following samples will be collected at baseline and subsequently every two months for 6 months: cervical, buccal, blood, fecal, urine and saliva samples. At the beginning and end of the study, participants will additionally receive sports medicine examinations (spirometry, ergometry/sports medicine exam) and an examination of vascular health. Participants are asked to complete an epidemiological questionnaire at the beginning of the study and receive additional questionnaires throughout the study to monitor food intake (prior to every visit), physical activity (once a month), or quality of life (baseline, 6 months). Participants may optionally donate skin biopsies at baseline and after 6 months.
Participants receive a fitness tracker to monitor physical activity and exercise in an objective manner. Some participants in the intermittent fasting group are receiving a capillary blood monitor to evaluate ketosis levels at the end of the fasting period three times a week.
Randomization in the intermittent fasting study arm: Participants are randomised to receive or to not receive ketogenic supplement 1:1 using menopause- and BMI-stratified block randomization.
Participant risks and benefits: Participants will receive support in implementing (putative) health-promoting interventions, including giving up smoking and intermittent fasting over 6 months, and are hence expected to personally benefit from participation. Risks are expected to be minimal as the study involves only a behavioural/lifestyle change, but can include e.g. development of haematoma after blood sampling, mood swings due to smoking cessation, or hunger at the initiation of intermittent fasting.
Sample size: Dynamics of DNA methylation changes are unknown at the start of the study, rendering sample size estimation challenging. For each study arm (intermittent fasting, intermittent fasting plus ketogenic supplement, smoking cessation) n=60 participants are recruited based on prior information of standard deviation in DNA methylation indices.
Expected Drop-Out levels: Based on prior literature in lifestyle or dietary interventions, drop-out rates of 15-20% are expected.
Data management and protection: Clinical data is recorded using an electronic case report form with validity checks. Laboratory data is analysed in a coded manner. Data protection follows the principles of the European General Data Protection Regulation (GDPR).
Quality control: Standard operating procedures for sample collection and clinical procedures have been designed and implemented.
- Conditions
- Healthy, Healthy Lifestyle, Smoking Cessation, Intermittent Fasting
- Being tested
- Smoking cessation, Intermittent fasting, Intermittent fasting with ketogenic supplement
- Keywords
- dna methylation, epigenetic age, intermittent fasting, smoking cessation, ketogenic supplement
- Medical subject headings
- Smoking Cessation, Intermittent Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Smoking cessationBehavioural
Smoking cessation encompasses three guided smoking cessation group therapy sessions (6-12 participants per session) followed by smoking cessation (occuring in the second session) for 6 months. Participants receive an optional exercise programme and motivational coaching over the duration of the study.
Intermittent fastingBehavioural
The dietary intervention encompasses induction (1 month) and maintenance (5 months) of a 16:8 intermittent fasting regime (time restricted eating to 8 h a day, fasting for remaining 16 h). During the introductory month, participants will only maintain a 14:10 intermittent fasting regime. Participants receive an optional exercise programme and motivational coaching over the duration of the study.
Intermittent fasting with ketogenic supplementBehavioural
The dietary intervention encompasses induction (1 month) and maintenance (5 months) of a 16:8 intermittent fasting regime (time restricted eating to 8 h a day, fasting for remaining 16 h). During the introductory month, participants will only maintain a 14:10 intermittent fasting regime. Participants receive a ketogenic supplement, medium-chain triglyceride fiber, to use daily. Participants receive an optional exercise programme and motivational coaching over the duration of the study.
| Study group | Role | What they receive |
|---|---|---|
| Smoking cessation | Experimental | Smoking cessation encompasses three guided smoking cessation group therapy sessions (6-12 participants per session) followed by smoking cessation (occuring in the second session) for 6 months. Participants receive an optional exercise programme and motivational coaching over the duration of the study. Receives: Behavioral: Smoking cessation |
| Diet intervention (intermittent fasting) | Experimental | The dietary intervention encompasses induction (1 month) and maintenance (5 months) of a 16:8 intermittent fasting regime (time restricted eating to 8 h a day, fasting for remaining 16 h). During the introductory month, participants will only maintain a 14:10 intermittent fasting regime. Participants are randomized to receive a ketogenic supplement, medium-chain triglyceride fiber, to use daily. Participants receive an optional exercise programme and motivational coaching over the duration of the study. Receives: Behavioral: Intermittent fasting; Behavioral: Intermittent fasting with ketogenic supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline scores of DNA methylation biomarkers of age, disease risk, and exposure
Examination of change in epigenetic age, disease risk, and exposure signature scores compared to baseline (before and after intervention, i.e. baseline-controlled) in cervical samples. DNA methylation levels will be measured using the Illumina MethylationEPIC array and computed using previously described methylation indices, including:
- WID-BC (Women's risk identification - Breast cancer)
- WID-OC (ovarian cancer)
- WID-EC (endometrial cancer)
- WID-CIN (cervical intraepithelial neoplasia)
- WID-REA (relative epithelial age)
- WID-RIA (relative immune age)
- pcgtAge (mitotic clock)
- WID-SOLA[ge] (systemic organ life age)
- WID-SMK (smoking)
Measured: Baseline, Month 6 (per participant)
Secondary outcomes (20)
Description of study characteristics: registration rate in percent (%)
Final registration rate of participants initially interested, i.e. those who signed up for information webinars, in percent (%)
Measured: Baseline
Description of study characteristics: drop-out rate in percent (%)
Number of included participants who dropped out over the course of the study, in percent (%)
Measured: Month 6 (Primary end point of study)
Description of study characteristics: compliance rate in percent (%)
Description of compliance rate (i.e. days compliant with the intervention over the duration of the study), in percent (%)
Measured: Month 6 (Primary end point of study)
Change in DNA methylation scores from baseline in cervical samples at month 2, month 4, and month 6
Examination of change in epigenetic age, disease risk, and exposure signature scores compared to baseline (before and after intervention, i.e. baseline-controlled) in cervical samples collected at baseline and again at month 2, 4, and 6, using t Tests and/or linear mixed-effects models where appropriate. DNA methylation levels will be measured using the Illumina MethylationEPIC array and computed using previously described methylation indices, including:
- WID-BC
- WID-OC
- WID-EC
- WID-CIN
- WID-REA (relative epithelial age)
- WID-RIA (relative immune age)
- pcgtAge (mitotic clock)
- WID-SOLA[ge]
- WID-SMK
The change in scores will also be compared to changes in the same scores in buccal and blood samples (outcomes 6 and 7) to evaluate temporal and spatial DNA methylation dynamics in response to lifestyle intervention.
Measured: Samples collected at baseline, month 2, month 4, and month 6
Change in DNA methylation scores from baseline in buccal samples at month 2, month 4, and month 6
Examination of change in epigenetic age, disease risk, and exposure signature scores compared to baseline (before and after intervention, i.e. baseline-controlled) in buccal samples collected at baseline and again at month 2, 4, and 6, using t Tests and/or linear mixed-effects models where appropriate. DNA methylation levels will be measured using the Illumina MethylationEPIC array and computed using previously described methylation indices, including:
- WID-BC
- WID-OC
- WID-EC
- WID-CIN
- WID-REA (relative epithelial age)
- WID-RIA (relative immune age)
- pcgtAge (mitotic clock)
- WID-SOLA[ge]
- WID-SMK
The change in scores will also be compared to changes in the same scores in cervical and blood samples (outcomes 5 and 7) to evaluate temporal and spatial DNA methylation dynamics in response to lifestyle intervention.
Measured: Samples collected at baseline, month 2, month 4, and month 6
Change in DNA methylation scores from baseline in blood samples at month 2, month 4, and month 6
Examination of change in epigenetic age, disease risk, and exposure signature scores compared to baseline (before and after intervention, i.e. baseline-controlled) in blood samples collected at baseline and again at month 2, 4, and 6, using t Tests and/or linear mixed-effects models where appropriate. DNA methylation levels will be measured using the Illumina MethylationEPIC array and computed using previously described methylation indices, including:
- WID-BC
- WID-OC
- WID-EC
- WID-CIN
- WID-REA (relative epithelial age)
- WID-RIA (relative immune age)
- pcgtAge (mitotic clock)
- WID-SOLA[ge]
- WID-SMK
The change in scores will also be compared to changes in the same scores in cervical and buccal samples (outcomes 5 and 6) to evaluate temporal and spatial DNA methylation dynamics in response to lifestyle intervention.
Measured: Samples collected at baseline, month 2, month 4, and month 6
Change in beneficial and harmful microbial species compared to baseline, in percent (%)
Quantification of selected beneficial and harmful bacteria based on previous literature, in fecal and saliva samples, and computation of change from baseline.
If big differences are found, temporal dynamics of changes will be examined in samples collected at month 2 and month 4.
Measured: Samples collected at baseline and month 6, optional month 2 and month 4
Change in microbial diversity score compared to baseline, in percent (%)
Quantification of microbial diversity using entropy scores at baseline and month 6. If big differences are found, temporal dynamics of changes will be examined in samples collected at month 2 and month 4.
Measured: Samples collected at baseline and month 6, optional month 2 and month 4
Change of immune and inflammatory cell populations in peripheral blood
Immune/inflammatory cell heterogeneity will be investigated in samples from peripheral blood using flow cytometry using well-established cellular markers. Cell population changes from baseline will be reported. If big differences are found, temporal dynamics of changes will be examined in samples collected at month 2 and month 4. Pending the outcome of this investigation, targeted investigation of associated plasma circulating markers may be conducted.
Measured: Samples collected at baseline and month 6, optional month 2 and month 4
Change in body mass index from baseline
Changes in BMI from baseline (diet arm of the study).
Changes in BMI from baseline (diet arm of the study).
Measured: Baseline and month 6.
Change in body composition as quantified by bioelectric impedance analysis from baseline
Change in body composition (% muscle, fat, water, abdominal fat composition) composition from baseline as quantified by bioelectric impedance analysis (diet arm of the study).
Measured: Baseline and month 6.
Change in smoking status from baseline
Changes in smoking status (smoking cessation arm of the study), defined as: smoking - yes/no.
Measured: Baseline and month 6.
Change in vascular health from baseline: pulse-wave velocity
Change in measured pulse wave velocity (m/s) as recorded using the vicorder.
Measured: Baseline and month 6.
Change in vascular health from baseline: intima-media thickness
Change in measured vascular intima-media thickness as measured using ultrasound.
Measured: Baseline and month 6.
Change in vascular health from baseline: intima-media thickness
Change in measured vascular plaque score as measured using ultrasound.
Measured: Baseline and month 6.
Change in physical activity from baseline
Change in physical activity from baseline, as quantified using the international physical activity questionnaire (IPAQ)
Measured: Baseline and month 6
Change in physical activity from baseline: fitness tracker data
Change in physical activity from baseline as quantified using fitness tracker data (resting heart rate month 0 to resting heart rate month 6)
Measured: Baseline and month 6
Change in physical activity from baseline: VO2max
Change in physical activity from baseline as quantified via sports examination (VO2max)
Measured: Baseline and month 6
Change in pulmonary health from baseline
Pulmonary health markers, e.g. FEV1 (Forced expiratory volume), at baseline and at 6 months using spirometry
Measured: Baseline and month 6
Change in health-related quality of life from baseline
Change in health-related quality of life (EuroQoL, i.e. EQ-5D-5L, https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/) at baseline and at 6 months
Measured: Baseline and month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2023
- Study start21 Apr 2021
- Primary completion31 Aug 2022
- Study completion4 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaet Innsbruck
- Sponsor type
- University, hospital or other
- Collaborators
- Tirol Kiniken GmbH
- Responsible party
- Principal investigator, Martin Widschwendter, Universitaet Innsbruck
- Investigators
- Martin Widschwendter, MD, Principal investigator, Universitaet Innsbruck
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05678426
- Sponsor's protocol ID
- TirolGESUND
- Other IDs
- 20210420-2560
- Acronym
- TirolGESUND
- Status last verified
- May 2026
- First submitted
- 16 Dec 2022
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets generated during and/or analysed during the current study, in particular epigenetic, metabolomic, and microbial will be stored in a publicly available but access-controlled repository (EGA-European Genome Phenome Archive, https://ega-archive.org/, or similar), due to the sensitive nature of epigenetic data. All data will only be shared in a coded (pseudonymised) or completely anonymised format. Prior to use, any potential collaborators must sign a data access agreement and comply with the terms of data sharing. Some datasets (summary characteristics, or completely anonymised results) may additionally be published as a supplement to the results publications.
Publications
GBD 2019 Cancer Risk Factors Collaborators. The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022 Aug 20;400(10352):563-591. doi: 10.1016/S0140-6736(22)01438-6.
PubMed 35988567Jacob L, Freyn M, Kalder M, Dinas K, Kostev K. Impact of tobacco smoking on the risk of developing 25 different cancers in the UK: a retrospective study of 422,010 patients followed for up to 30 years. Oncotarget. 2018 Apr 3;9(25):17420-17429. doi: 10.18632/oncotarget.24724. eCollection 2018 Apr 3.
PubMed 29707117Key TJ, Allen NE, Spencer EA, Travis RC. The effect of diet on risk of cancer. Lancet. 2002 Sep 14;360(9336):861-8. doi: 10.1016/S0140-6736(02)09958-0.
PubMed 12243933Steck SE, Murphy EA. Dietary patterns and cancer risk. Nat Rev Cancer. 2020 Feb;20(2):125-138. doi: 10.1038/s41568-019-0227-4. Epub 2019 Dec 17.
PubMed 31848467Barrett JE, Herzog C, Jones A, Leavy OC, Evans I, Knapp S, Reisel D, Nazarenko T, Kim YN, Franchi D, Ryan A, Franks J, Bjorge L, Zikan M, Cibula D, Harbeck N, Colombo N, Dudbridge F, Jones L, Sundstrom K, Dillner J, Radestad AF, Gemzell-Danielsson K, Pashayan N, Widschwendter M. The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples. Nat Commun. 2022 Feb 1;13(1):449. doi: 10.1038/s41467-021-27918-w.
PubMed 35105882Barrett JE, Sundstrom K, Jones A, Evans I, Wang J, Herzog C, Dillner J, Widschwendter M. The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer. Genome Med. 2022 Oct 19;14(1):116. doi: 10.1186/s13073-022-01116-9.
PubMed 36258199Barrett JE, Jones A, Evans I, Reisel D, Herzog C, Chindera K, Kristiansen M, Leavy OC, Manchanda R, Bjorge L, Zikan M, Cibula D, Widschwendter M. The DNA methylome of cervical cells can predict the presence of ovarian cancer. Nat Commun. 2022 Feb 1;13(1):448. doi: 10.1038/s41467-021-26615-y.
PubMed 35105887Barrett JE, Herzog C, Kim YN, Bartlett TE, Jones A, Evans I, Cibula D, Zikan M, Bjorge L, Harbeck N, Colombo N, Howell SJ, Radestad AF, Gemzell-Danielsson K, Widschwendter M. Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock. Genome Biol. 2022 Feb 22;23(1):52. doi: 10.1186/s13059-022-02603-3.
PubMed 35189945
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TirolGESUND: General Exercise, Smoking Undone, and Nutrition Diet
- ClinicalTrials.gov ID
- NCT05678426
- Acronym / sponsor ID
- TirolGESUND / TirolGESUND
- Conditions
- Healthy, Healthy Lifestyle, Smoking Cessation, Intermittent Fasting
- Keywords
- dna methylation, epigenetic age, intermittent fasting, smoking cessation, ketogenic supplement
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Universitaet InnsbruckUniversity, hospital or other
- Collaborators
- Tirol Kiniken GmbH
- Study start
- 21 Apr 2021 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 4 Sep 2025 (actual)
- First posted
- 10 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical study is to learn about disease-risk and age-associated changes in DNA methylation patterns associated with disease risk or age in healthy women aged 30-60 in response to health-promoting lifestyle intervention (intermittent fasting or smoking cessation). The main questions the study aims to answer are:
- Are the scores of DNA methylation in epigenetic signatures associated with age, women's cancer risk, or risk exposure reduced after 6 months of lifestyle intervention compared to baseline?
- What are the dynamics of DNA methylation changes during or following intervention, and do differences in changes between different sample types exist?
- Which other biomarkers of health and disease, including metabolic changes, microbiome, clinical, mental, or inflammatory parameters, are altered following intervention?
The investigators also aim to explore whether DNA methylation changes are associated with changes in other biomarkers mentioned above.
Participants will be allocated to intermittent fasting or smoking cessation based on inclusion criteria. Intermittent fasting encompasses a 16:8 intermittent fasting schedule. Food intake is limited to an 8 h window per day with fasting for the remaining 16 h. Within the intermittent fasting study, participants are randomised to receive a ketogenic supplement (medium-chain triglyceride fibre) or not. Participants in the smoking cessation study will be guided to stop smoking. All participants will receive 1:1 personal coaching throughout the study, and will be provided with an optional exercise programme. All participants will also receive nutritional advice from a professional dietician throughout the study. Participants are invited to donate samples every 2 months for 6 months.
Researchers will compare signatures at the start and after 6 months of intervention. Within the intermittent fasting group, researchers will compare effects in individuals that received the ketogenic supplement to those that did not.
Detailed description
Background and study aims: A recent study reported that a majority of malignancies may be caused modifiable risk factors and could therefore be prevented. Smoking and diet are known risk factors for cancer but also other disorders such as cardiovascular or metabolic disorders and neurodegeneration, and may promote premature cellular ageing. The investigators and others have recently described epigenetic signatures for risk of being diagnosed, or developing future, women's cancers, as well as signatures reflecting cellular ageing and exposure to risk factors such as smoking. Utilization of DNA methylation biomarkers as surrogate endpoints indicative of current and/or future disease risk could improve future efforts in preventive medicine, both by providing information on disease risk and biofeedback. Few longitudinal studies have so far investigated the effects of lifestyle changes on DNA methylation and other biomarkers of health and disease.
TirolGESUND investigates the effect of two lifestyle interventions, smoking cessation or intermittent fasting (both with additional optional exercise), over 6 months for the promotion of health and reduction of disease risk, focusing on women's cancers.
Hypothesis: Intermittent fasting or smoking cessation for a duration of 6 months result in a modulation of scores of disease risk- and age-associated DNA methylation biomarker signatures in cervical samples, indicating a reduction of disease risk, exposure, or cellular ageing.
Study design: TirolGESUND is a baseline-controlled intervention study with two parallel arms, smoking cessation and intermittent fasting. Participants are allocated to the study arm based on eligibility criteria. Within the intermittent fasting arm, participants are randomised to receive a ketogenic supplement or not. Ketosis has been suggested to elicit beneficial metabolic alterations and could therefore further enhance beneficial effects in the dietary intervention.
Endpoints: The primary endpoint are score changes in epigenetic biomarkers of cellular ageing and disease risk, primarily recently published Women's cancer risk identification (WID) indices.
In secondary and subsidiary outcomes, the study will explore temporal and spatial dynamics of DNA methylation alterations in response to lifestyle interventions, comparing different surrogate samples (blood, buccal, cervical).
The study also investigates the impact of lifestyle intervention on other biomarkers of health and disease as a pilot study for future behavioural studies in the space of disease prevention and ageing research.
Intervention: Participants will be allocated to intermittent fasting or smoking cessation based on inclusion criteria. Intermittent fasting encompasses a 16:8 intermittent fasting schedule. Food intake is limited to an 8 h window per day with fasting for the remaining 16 h. Within the intermittent fasting study, participants are randomised to receive a ketogenic supplement (medium-chain triglyceride fibre) or not. Participants in the smoking cessation study will be guided to stop smoking. All participants will receive 1:1 personal coaching throughout the study, and will be provided with an optional exercise programme. All participants will also receive nutritional advice from a professional dietician throughout the study.
The duration of the study including intervention is 6 months for each participant. Participants are invited to return for optional sample collection visits at 12 and 18 months.
Visits and examinations: The following samples will be collected at baseline and subsequently every two months for 6 months: cervical, buccal, blood, fecal, urine and saliva samples. At the beginning and end of the study, participants will additionally receive sports medicine examinations (spirometry, ergometry/sports medicine exam) and an examination of vascular health. Participants are asked to complete an epidemiological questionnaire at the beginning of the study and receive additional questionnaires throughout the study to monitor food intake (prior to every visit), physical activity (once a month), or quality of life (baseline, 6 months). Participants may optionally donate skin biopsies at baseline and after 6 months.
Participants receive a fitness tracker to monitor physical activity and exercise in an objective manner. Some participants in the intermittent fasting group are receiving a capillary blood monitor to evaluate ketosis levels at the end of the fasting period three times a week.
Randomization in the intermittent fasting study arm: Participants are randomised to receive or to not receive ketogenic supplement 1:1 using menopause- and BMI-stratified block randomization.
Participant risks and benefits: Participants will receive support in implementing (putative) health-promoting interventions, including giving up smoking and intermittent fasting over 6 months, and are hence expected to personally benefit from participation. Risks are expected to be minimal as the study involves only a behavioural/lifestyle change, but can include e.g. development of haematoma after blood sampling, mood swings due to smoking cessation, or hunger at the initiation of intermittent fasting.
Sample size: Dynamics of DNA methylation changes are unknown at the start of the study, rendering sample size estimation challenging. For each study arm (intermittent fasting, intermittent fasting plus ketogenic supplement, smoking cessation) n=60 participants are recruited based on prior information of standard deviation in DNA methylation indices.
Expected Drop-Out levels: Based on prior literature in lifestyle or dietary interventions, drop-out rates of 15-20% are expected.
Data management and protection: Clinical data is recorded using an electronic case report form with validity checks. Laboratory data is analysed in a coded manner. Data protection follows the principles of the European General Data Protection Regulation (GDPR).
Quality control: Standard operating procedures for sample collection and clinical procedures have been designed and implemented.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Smoking cessation | Experimental | Behavioral: Smoking cessationSmoking cessation encompasses three guided smoking cessation group therapy sessions (6-12 participants per session) followed by smoking cessation (occuring in the second session) for 6 months. Participants receive an optional exercise programme and motivational coaching over the duration of the study. |
| Diet intervention (intermittent fasting) | Experimental | Behavioral: Intermittent fasting, Behavioral: Intermittent fasting with ketogenic supplementThe dietary intervention encompasses induction (1 month) and maintenance (5 months) of a 16:8 intermittent fasting regime (time restricted eating to 8 h a day, fasting for remaining 16 h). During the introductory month, participants will only maintain a 14:10 intermittent fasting regime. Participants are randomized to receive a ketogenic supplement, medium-chain triglyceride fiber, to use daily. Participants receive an optional exercise programme and motivational coaching over the duration of the study. |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Women aged 30 to 60
- Motivated to change their lifestyle
- 3a. Smoking cessation: ≥10 cigarettes per day for at least the last five years
- 3b Dietary intervention: BMI between 25 and 35
- NB [Nota Bene], should 3a and 3b apply, participant will be allocated to the smoking cessation intervention.
Key exclusion criteria (9 listed)
- Relevant underlying conditions:
- Current pregnancy or lactation period
- Total hysterectomy
- Known current or previous premalignant lesion of the cervix uteri (CIN2/3)
- Concurrent participation in another interventional trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Smoking cessationSmoking cessation encompasses three guided smoking cessation group therapy sessions (6-12 participants per session) followed by smoking cessation (occuring in the second session) for 6 months. Participants receive an optional exercise programme and motivational coaching over the duration of the study. | Behavioural | Smoking cessation |
| Intermittent fastingThe dietary intervention encompasses induction (1 month) and maintenance (5 months) of a 16:8 intermittent fasting regime (time restricted eating to 8 h a day, fasting for remaining 16 h). During the introductory month, participants will only maintain a 14:10 intermittent fasting regime. Participants receive an optional exercise programme and motivational coaching over the duration of the study. | Behavioural | Diet intervention (intermittent fasting) |
| Intermittent fasting with ketogenic supplementThe dietary intervention encompasses induction (1 month) and maintenance (5 months) of a 16:8 intermittent fasting regime (time restricted eating to 8 h a day, fasting for remaining 16 h). During the introductory month, participants will only maintain a 14:10 intermittent fasting regime. Participants receive a ketogenic supplement, medium-chain triglyceride fiber, to use daily. Participants receive an optional exercise programme and motivational coaching over the duration of the study. | Behavioural | Diet intervention (intermittent fasting) |
Primary outcome
Change from baseline scores of DNA methylation biomarkers of age, disease risk, and exposure
Time frame: Baseline, Month 6 (per participant)
Examination of change in epigenetic age, disease risk, and exposure signature scores compared to baseline (before and after intervention, i.e. baseline-controlled) in cervical samples. DNA methylation levels will be measured using the Illumina MethylationEPIC array and computed using previously described methylation indices, including: * WID-BC (Women's risk identification - Breast cancer) * WID-OC (ovarian cancer) * WID-EC (endometrial cancer) * WID-CIN (cervical intraepithelial neoplasia) * WID-REA (relative epithelial age) * WID-RIA (relative immune age) * pcgtAge (mitotic clock) * WID-SOLA[ge] (systemic organ life age) * WID-SMK (smoking)
20 secondary outcomes
Description of study characteristics: registration rate in percent (%)
Time frame: Baseline
Description of study characteristics: drop-out rate in percent (%)
Time frame: Month 6 (Primary end point of study)
Description of study characteristics: compliance rate in percent (%)
Time frame: Month 6 (Primary end point of study)
Change in DNA methylation scores from baseline in cervical samples at month 2, month 4, and month 6
Time frame: Samples collected at baseline, month 2, month 4, and month 6
Change in DNA methylation scores from baseline in buccal samples at month 2, month 4, and month 6
Time frame: Samples collected at baseline, month 2, month 4, and month 6
Change in DNA methylation scores from baseline in blood samples at month 2, month 4, and month 6
Time frame: Samples collected at baseline, month 2, month 4, and month 6
Change in beneficial and harmful microbial species compared to baseline, in percent (%)
Time frame: Samples collected at baseline and month 6, optional month 2 and month 4
Change in microbial diversity score compared to baseline, in percent (%)
Time frame: Samples collected at baseline and month 6, optional month 2 and month 4
Change of immune and inflammatory cell populations in peripheral blood
Time frame: Samples collected at baseline and month 6, optional month 2 and month 4
Change in body mass index from baseline
Time frame: Baseline and month 6.
Change in body composition as quantified by bioelectric impedance analysis from baseline
Time frame: Baseline and month 6.
Change in smoking status from baseline
Time frame: Baseline and month 6.
Change in vascular health from baseline: pulse-wave velocity
Time frame: Baseline and month 6.
Change in vascular health from baseline: intima-media thickness
Time frame: Baseline and month 6.
Change in vascular health from baseline: intima-media thickness
Time frame: Baseline and month 6.
Change in physical activity from baseline
Time frame: Baseline and month 6
Change in physical activity from baseline: fitness tracker data
Time frame: Baseline and month 6
Change in physical activity from baseline: VO2max
Time frame: Baseline and month 6
Change in pulmonary health from baseline
Time frame: Baseline and month 6
Change in health-related quality of life from baseline
Time frame: Baseline and month 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Background: PubMed 35988567GBD 2019 Cancer Risk Factors Collaborators. The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022 Aug 20;400(10352):563-591. doi: 10.1016/S0140-6736(22)01438-6.
- Background: PubMed 29707117Jacob L, Freyn M, Kalder M, Dinas K, Kostev K. Impact of tobacco smoking on the risk of developing 25 different cancers in the UK: a retrospective study of 422,010 patients followed for up to 30 years. Oncotarget. 2018 Apr 3;9(25):17420-17429. doi: 10.18632/oncotarget.24724. eCollection 2018 Apr 3.
- Background: PubMed 12243933Key TJ, Allen NE, Spencer EA, Travis RC. The effect of diet on risk of cancer. Lancet. 2002 Sep 14;360(9336):861-8. doi: 10.1016/S0140-6736(02)09958-0.
- Background: PubMed 31848467Steck SE, Murphy EA. Dietary patterns and cancer risk. Nat Rev Cancer. 2020 Feb;20(2):125-138. doi: 10.1038/s41568-019-0227-4. Epub 2019 Dec 17.
- Background: PubMed 35105882Barrett JE, Herzog C, Jones A, Leavy OC, Evans I, Knapp S, Reisel D, Nazarenko T, Kim YN, Franchi D, Ryan A, Franks J, Bjorge L, Zikan M, Cibula D, Harbeck N, Colombo N, Dudbridge F, Jones L, Sundstrom K, Dillner J, Radestad AF, Gemzell-Danielsson K, Pashayan N, Widschwendter M. The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples. Nat Commun. 2022 Feb 1;13(1):449. doi: 10.1038/s41467-021-27918-w.
- Background: PubMed 36258199Barrett JE, Sundstrom K, Jones A, Evans I, Wang J, Herzog C, Dillner J, Widschwendter M. The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer. Genome Med. 2022 Oct 19;14(1):116. doi: 10.1186/s13073-022-01116-9.
- Background: PubMed 35105887Barrett JE, Jones A, Evans I, Reisel D, Herzog C, Chindera K, Kristiansen M, Leavy OC, Manchanda R, Bjorge L, Zikan M, Cibula D, Widschwendter M. The DNA methylome of cervical cells can predict the presence of ovarian cancer. Nat Commun. 2022 Feb 1;13(1):448. doi: 10.1038/s41467-021-26615-y.
- Background: PubMed 35189945Barrett JE, Herzog C, Kim YN, Bartlett TE, Jones A, Evans I, Cibula D, Zikan M, Bjorge L, Harbeck N, Colombo N, Howell SJ, Radestad AF, Gemzell-Danielsson K, Widschwendter M. Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock. Genome Biol. 2022 Feb 22;23(1):52. doi: 10.1186/s13059-022-02603-3.
- Individual participant dataSharing planned: Yes. The datasets generated during and/or analysed during the current study, in particular epigenetic, metabolomic, and microbial will be stored in a publicly available but access-controlled repository (EGA-European Genome Phenome Archive, https://ega-archive.org/, or similar), due to the sensitive nature of epigenetic data. All data will only be shared in a coded (pseudonymised) or completely anonymised format. Prior to use, any potential collaborators must sign a data access agreement and comply with the terms of data sharing. Some datasets (summary characteristics, or completely anonymised results) may additionally be published as a supplement to the results publications.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Widschwendter, MD principal investigator
Universitaet Innsbruck
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Smoking cessation, Intermittent fasting and Intermittent fasting with ketogenic supplement in people with Healthy and Healthy Lifestyle, run by Universitaet Innsbruck at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline scores of DNA methylation biomarkers of age, disease risk, and exposure (time frame: Baseline, Month 6 (per participant)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05678426, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.