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

NCT05678426 | Completed

• 2 other identifiers: TirolGESUND20210420-2560
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Healthy; Healthy Lifestyle; Smoking Cessation; Intermittent Fasting

Keywords

dna methylation; epigenetic age; intermittent fasting; smoking cessation; ketogenic supplement

Outcome Measures

Primary Outcomes (1)

• 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)

  Baseline, Month 6 (per participant)

Secondary Outcomes (20)

• Description of study characteristics: registration rate in percent (%)

  Baseline

• Description of study characteristics: drop-out rate in percent (%)

  Month 6 (Primary end point of study)

• Description of study characteristics: compliance rate in percent (%)

  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

  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

  Samples collected at baseline, month 2, month 4, and month 6

Other Outcomes (2)

• Exploratory investigation of metabolic profile via NMR over course of intervention for hypothesis generation

  Urine and saliva samples collected at baseline, month 2, month 4, and month 6

• Change of plasma inflammatory markers compared to baseline.

  Samples collected at baseline and month 6, optional month 2 and month 4

Study Arms (2)

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.

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.

Behavioral: Intermittent fasting; Behavioral: Intermittent fasting with ketogenic supplement

Interventions

Smoking cessation BEHAVIORAL

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.

Smoking cessation

Intermittent fasting BEHAVIORAL

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.

Diet intervention (intermittent fasting)

Intermittent fasting with ketogenic supplement BEHAVIORAL

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.

Diet intervention (intermittent fasting)

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 30 to 60
• Motivated to change their lifestyle
• Smoking cessation intervention:
• a. Smoking cessation: ≥10 cigarettes per day for at least the last five years
• Dietary intervention:
• b Dietary intervention: BMI between 25 and 35
• NB \[Nota Bene\], should 3a and 3b apply, participant will be allocated to the smoking cessation intervention.

You may not qualify if:

• 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
• Total hysterectomy
• Known current or previous premalignant lesion of the cervix uteri (CIN2/3)
• Concurrent participation in another interventional trial

Sponsors & Collaborators

• Universitaet Innsbruck: lead
• Tirol Kiniken GmbH: collaborator

Study Sites (1)

European Translational Oncology Prevention and Screening Institute

Hall in Tirol, Tyrol, 6060, Austria

Location

Related Publications (8)

• 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.

  PMID: 35988567 BACKGROUND

• Jacob 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.

  PMID: 29707117 BACKGROUND

• Key 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.

  PMID: 12243933 BACKGROUND

• Steck 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.

  PMID: 31848467 BACKGROUND

• Barrett 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.

  PMID: 35105882 BACKGROUND

• Barrett 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.

  PMID: 36258199 BACKGROUND

• Barrett 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.

  PMID: 35105887 BACKGROUND

• Barrett 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. Erratum In: Genome Biol. 2022 Jun 29;23(1):142. doi: 10.1186/s13059-022-02704-z.

  PMID: 35189945 BACKGROUND

MeSH Terms

Conditions

Smoking Cessation; Intermittent Fasting

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Fasting; Feeding Behavior

Study Officials

• Martin Widschwendter, MD

  Universitaet Innsbruck

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Coordinator/Co-Principal Investigator

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: January 10, 2023
• Study Start: April 21, 2021
• Primary Completion: August 31, 2022
• Study Completion: September 4, 2025
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR, ANALYTIC CODE
• Time Frame: Data will be deposited when summary data are published.
• Access Criteria: Data will be restricted for non-commercial research in the space of healthy ageing research. Sharing is restricted to certain geographical areas that have high GDPR standards.

Locations

AU (1)