The Impact of Time-restricted Eating on the Outcomes Associated With Polycystic Ovary Syndrome

NCT06204965 | Unknown

• 1 other identifier: 646/23
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Polycystic Ovary Syndrome (PCOS) is a disorder that affects approximately 10-15% of women of reproductive age. Increased activity of the hypothalamic-pituitary-ovarian (HPO) axis is considered to be one of the main factors associated with the pathogenesis of PCOS. The regulation of the activity of this axis is influenced by the following factors: insulin resistance and the activity of kisspeptins in the hypothalamus. It is suggested that intestinal dysbiosis may also play a key role in the pathogenesis of PCOS. It was noticed that the presence of bacteria producing gamma-aminobutyric acid in the intestine is positively correlated with the concentration of luteinizing hormone (LH) in the serum, which indicates the relationship between the functioning of the gut-brain axis and PCOS. A dysbiotic factor is an incorrect diet and inappropriate timing of its consumption, which may also lead to inhibition of kisspeptin expression in the hypothalamus and cause menstrual disorders. Due to the fact that most obese women with PCOS eat significantly more meals in the second part of the day, and these meals are characterized by a significant supply of fat and simple sugars, intestinal dysbiosis seems to be an important cause of the observed disorders, while the use of chrononutrition, consisting in synchronizing meal times with endogenous 24-hour circadian rhythms may partially restore eubiosis in the intestine and improve the reproductive, metabolic and neurohormonal health of women with PCOS. Time-restricted feeding (TRF), which involves eating food usually within 8 hours followed by 16 hours of fasting, seems to be a regime that allows restoring eubiosis in the intestinal microbiota and improving the quality of life of women with PCOS. So far, only one study has been conducted among women with PCOS who used TRF for 5 weeks and a number of positive changes were demonstrated (hormonal or metabolic). However, this study did not include an assessment of the microbial and neurohormonal parameters, which seems to be a key issue. Taking the above into account, it was hypothesized that TRF may be an appropriate therapeutic tool for women with PCOS, which will positively affect metabolic and hormonal parameters by changing the composition of the intestinal microbiota. Therefore, the main aim of the experiment is to investigate the impact of TRF on the composition of the intestinal microbiota, its metabolites, and metabolic and neurohormonal parameters in women with PCOS.

Conditions

Polycystic Ovary Syndrome

Keywords

Intermittent Fasting; Microbiota; Neurotransmitter Agents; Polycystic Ovary Syndrome

Outcome Measures

Primary Outcomes (7)

• Change in body weight

  Body weight measurement in a standing position, without shoes, in light clothing, on an electronic scale with an accuracy of 0.1 kg.

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in circumferences

  Waist and hip measurements will be taken using an elastic tape. Waist circumference measurement - the tape is placed horizontally or slightly obliquely halfway between the lower edge of the ribs and the upper crest of the ilium. Measurement performed during apnea.

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in body composition

  Body composition will be measured using dual-energy X-ray absorptiometry (DXA) as a method that uses the phenomenon of weakening the beam of ionizing radiation passing through tissues of various densities. This method is safe and non-invasive. The mass of adipose tissue, including visceral fat tissue, the mass of lean tissue are measured (expressed in the same unit - kilograms)

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in composition of the intestinal microbiota

  Participants will be asked to provide stool samples at each scheduled meeting. Detailed instructions on sample collection and transport will be provided by the people conducting the study, and participants will receive containers containing preservative liquid. Bacterial DNA will be isolated from the provided stool samples using the QIAmp Fast DNA Stool Mini Kit. Then, the DNA will be properly secured and sent to an external company, Genomed S.A. (Warsaw, Poland), in which the assessment of microbiota will be carried out by metagenomic 16s rRNA sequencing using the V3-V4 region. Then, a bioinformatics analysis will be performed in the R environment using packages such as phyloseq, vegan, microbiome.

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in selected hormonal parameters

  Blood will be collected four times from the antecubital vein on an empty stomach, into test tubes with clotting granules (a single sample will amount to a total of 18 ml). The serum will be obtained by centrifugation of a venous blood clot. Hormonal parameters (FSH, LH, testosterone, SHBG), will be performed using the ELISA enzyme-linked immunosorbent assay (expressed in the same unit - pg/ml)

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in lipid profile

  Blood will be collected four times from the antecubital vein on an empty stomach, into test tubes with clotting granules (a single sample will amount to a total of 18 ml). The serum will be obtained by centrifugation of a venous blood clot. Total cholesterol (T-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides concentrations will be determined using the Thermo Scientific Konelab 20i automatic biochemical analyzer (enzymatic method ). The nonHDL-C parameter will be calculated using the formula: nonHDL-C = T-C - HDL-C (expressed in the same unit - mg/dl or mmol/l).

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in glucose metabolism

  Blood will be collected four times from the antecubital vein on an empty stomach, into test tubes with clotting granules (a single sample will amount to a total of 18 ml). The serum will be obtained by centrifugation of a venous blood clot. Insulin concentration will be performed using the ELISA enzyme-linked immunosorbent assay, while glucose will be determined using the Thermo Scientific Konelab 20i automatic biochemical analyzer (enzymatic method ) (expressed in the same unit - mg/dl or mmol/l).

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

Secondary Outcomes (6)

• Assessment of changes in eating behavior pre- and post-intervention

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in bone density

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in the concentration of short-chain fatty acids in feces

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in the expression of genes encoding kisspeptin and gamma-aminobutyric acid

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

• Change in intestinal barrier integrity

  Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)

Study Arms (2)

Time-restricted eating group (TRE group)

EXPERIMENTAL

Participants assigned to the TRE group will be instructed to continue eating their usual diet during the experiment (without any qualitative or quantitative restrictions), but to eat it within a limited time frame - from 9:00 a.m. to 5:00 p.m., and then fast until the next day ( protocol 8/16).

Behavioral: Time-restricted eating

Non-fasting group

NO INTERVENTION

Participants assigned to the control group will receive only dietary recommendations consistent with the healthy eating plate. Additionally, the recommended energy intake will be individually determined for each patient using the PPM (calculated using the Harris-Benedict formula) multiplied by the physical activity factor.

Interventions

Time-restricted eating BEHAVIORAL

Time-restricted eating (TRE) is a dietary pattern where food intake is restricted to 8 hours of the day with no limitation on nutrient quality or quantity. Participants assigned to the intervention group will eat their usual diet from 9:00 a.m. to 5:00 p.m., and then fast until the next day (protocol 8/16). During the 16-hour fast, only hot and cold drinks will be allowed, i.e. coffee, tea or tea and water, but all products and dishes with energy value (including coffee cream, sweet teas, alcohol, snacks, etc.) will be prohibited. The TRE protocol will be implemented 7 days a week for a period of 3 months (12 weeks).

Time-restricted eating group (TRE group)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-40
• suffering from Polycystic Ovary Syndrome, confirmed by appropriate medical documentation
• BMI \>25 kg\^m2

You may not qualify if:

• Taking medications regulating carbohydrate, lipid as well as medications affecting body weight in the last 3 months (will be assessed during a general medical interview conducted by Jakub Noskiewicz, MD, PhD)
• Taking antibiotics in the last 3 months
• Smoking in the last 3 months and alcohol consumption \>100 g per week
• Competitive sports practice
• Significant body weight fluctuations in the 3 months before the start of the study (\>5%)
• Pregnant or breastfeeding women
• BMI \<25 kg\^m2

Sponsors & Collaborators

• Joanna Bajerska: lead

Study Sites (1)

Poznań University of Life Sciences

Poznan, Greater Poland Voivodeship, 60-637, Poland

RECRUITING

Related Publications (5)

• Li C, Xing C, Zhang J, Zhao H, Shi W, He B. Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome. J Transl Med. 2021 Apr 13;19(1):148. doi: 10.1186/s12967-021-02817-2.

  PMID: 33849562 BACKGROUND

• Torres PJ, Ho BS, Arroyo P, Sau L, Chen A, Kelley ST, Thackray VG. Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model. Endocrinology. 2019 May 1;160(5):1193-1204. doi: 10.1210/en.2019-00050.

  PMID: 30924862 BACKGROUND

• Liao B, Qiao J, Pang Y. Central Regulation of PCOS: Abnormal Neuronal-Reproductive-Metabolic Circuits in PCOS Pathophysiology. Front Endocrinol (Lausanne). 2021 May 28;12:667422. doi: 10.3389/fendo.2021.667422. eCollection 2021.

  PMID: 34122341 BACKGROUND

• Tremellen K, Pearce K. Dysbiosis of Gut Microbiota (DOGMA)--a novel theory for the development of Polycystic Ovarian Syndrome. Med Hypotheses. 2012 Jul;79(1):104-12. doi: 10.1016/j.mehy.2012.04.016. Epub 2012 Apr 27.

  PMID: 22543078 BACKGROUND

• Minabe S, Iwata K, Tsuchida H, Tsukamura H, Ozawa H. Effect of diet-induced obesity on kisspeptin-neurokinin B-dynorphin A neurons in the arcuate nucleus and luteinizing hormone secretion in sex hormone-primed male and female rats. Peptides. 2021 Aug;142:170546. doi: 10.1016/j.peptides.2021.170546. Epub 2021 Mar 29.

  PMID: 33794282 BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Intermittent Fasting

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Fasting; Feeding Behavior; Behavior

Study Officials

• Agata Chmurzyńska, Prof.

  Department of Human Nutrition and Dietetics, Poznań University of Life Sciences

  STUDY CHAIR

Central Study Contacts

Joanna Bajerska, Assoc. Prof.

CONTACT

8466056; Joanna.bajerska@up.poznan.pl

Joanna M Pieczyńska-Zając, M.Sc.

CONTACT

660950786; joanna.pieczynska@up.poznan.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: Women with Polycystic Ovary Syndrome (n=52), aged 18-40.

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: January 12, 2024
• Study Start: December 12, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD data will be made available after publication of all planned articles presenting the results of the planned experiment for a period of 10 years.
• Access Criteria: All persons having access to data have to be authorised to process personal data. A secured work e-mail is used for correspondence. Access to collected and processed sensitive data will be limited solely to the group of authorised users. The Head of the project authorises individuals to have access to data. The e-mail requesting access to the IPD should include your name and surname, academic degree and affiliation. Data will only be made available after the person's identity has been verified and the purpose of using the data is clear (e.g. meta-analysis). Then, the data owner will verify the need to have the data and send it in a password-protected form. All data will be pseudonymized.

Locations

PL (1)