Clinical trial NCT05126199: Time-restricted Eating to Improve Metabolic Abnormalities in Polycystic Ovarian Syndrome
Official title: The Effect of Time-restricted Eating on Insulin Levels and Other Metabolic Abnormalities in Polycystic Ovarian Syndrome: A Randomised Feasibility Study of Real-world Clinical Advice
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: PCOS
Hyperinsulinemia
Insulin Resistance
Keywords: PCOS
Intermittent Fasting
Fasting
Hyperinsulinemia
Insulin Resistance
Lead sponsor: Tallaght University Hospital
Sponsor class: OTHER
Collaborators: name: Tallaght University Hospital
First posted: 2021-11-18
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Polycystic ovarian syndrome (PCOS) is associated with metabolic symptoms such as hyperinsulinemia. Time-restricted eating may reduce serum insulin and improve insulin resistance in patients with PCOS. Currently, there are few studies investigating time-restricted eating in patients with PCOS. The investigators plan to test the feasibility of time-restricted eating in the management of PCOS by means of a real-world clinical intervention. The investigators will determine if an 18:6 eating protocol reduces insulin levels by means of a randomised controlled crossover trial.

Detailed description: Background: Polycystic ovarian syndrome (PCOS) is the most common reproductive endocrinopathy in women of reproductive age with many associated metabolic symptoms, in particular hyperinsulinemia, insulin resistance and a high lifetime risk of type 2 diabetes mellitus. The effects of time-restricted eating on metabolic profiles have been investigated in many endocrinopathies, but there are minimal data in PCOS.

Methods: This study will investigate the feasibility of time-restricted eating in the management of PCOS, and its effects on insulin levels and other metabolic parameters.

To achieve this, the investigators will recruit 20 patients with PCOS (normal weight, overweight, obese).

In a randomised cross-over design, participants will be observed for two consecutive 12 week periods (with a 4 weeks washout period in between) following either 'time-restricted eating' or 'usual eating', detailed below.

1. 18:6 protocol: 18 hours of fasting and a 6-hours eating window, with no other specific dietary advice. Participants choose their own 6-hour period according to their lifestyle and preference.
2. Usual eating: follow usual eating patterns, no time restriction, no other dietary advice

When fasting, participants are permitted to consume plain water, unflavoured/unsweetened sparkling water, black breakfast tea and black coffee.

Dietary intake will be determined at baseline, at midpoint of each study arm, and at the end of the study using Nutritics software. Participants will self-record dietary intake using the Nutritics 'app'.

The primary endpoints will be serum insulin and feasibility of the intervention as well as safety, acceptability, and compliance with time-restricted eating.

Secondary endpoints will be insulin resistance (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), androgens (testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, 17-Hydroxyprogesterone (17-OHP) and sex hormone binding globulin (SHBG)), appetite (10-point visual analogue scale), hunger/satiety (glucagon-like peptide 1 (GLP-1), grehlin, PYY and oxyntomodulin, fasting glucose, HbA1c, lipid profile, lipoprotein lipid A, apolipoprotein A1, apolipoprotein B, anthropometrics (weight, body mass index, hip and waist circumference), dietary intake (calorie and macronutrient intake; micronutrient intake including iron, calcium; dietary pattern including timing).

Results: Safety and acceptability will be measured by adverse event reporting and measurement of adherence. Paired t-test will be used to assess between baseline and post intervention measurements. Results considered statistically significant if p\<0.05.

Discussion: Time-restricted eating has potential to aid in improvement of insulin resistance in patients with PCOS based on studies in other populations. There is no substantial literature on this subject to date in the PCOS patient cohort, with this being the first randomised study to date. The investigators will discuss the effects of time-restricted eating on insulin levels in the specific population of women with PCOS based on the results.

Eligibility criteria: Inclusion Criteria:

* Adult women of reproductive age with confirmed diagnosis of PCOS (Rotterdam Criteria, including at least 2 of 3 characteristics: oligomenorrhea, clinical and/or biochemical hyperandrogenism and ultrasound criteria)
* No BMI restriction
* Able and willing to provide explicit, informed consent

Exclusion Criteria:

* Type 1 diabetes, medication-controlled type 2 diabetes
* Pregnancy
* Currently participating in weight loss programme, or reported weight change in last 3 months (\>5% of current body weight)
* Documented history of eating disorder
* Ovulation medication, such as clomiphene citrate
* Weight loss medication affecting weight or appetite in last 6 months, including weight loss medications, antipsychotic drugs or other medications as determine by the physician (eg. Semaglutide, liraglutide, orlistat, amphetamines, Qsymia (phentermine-topiramate), bupropion-naltrexone (Contrave))
* Known liver, renal or thyroid dysfunction (not including non-alcoholic fatty liver disease with hypothyroidism on treatment or subclinical hypothyroidism seen in a large proportion of patients with PCOS)
* Unable to participate in follow-up for at least 24 weeks
* Unable or unwilling to provide explicit, informed consent

Primary outcomes:
measure: Drop-out rate
timeFrame: 6 weeks
measure: Drop-out rate
timeFrame: 12 weeks
measure: Adverse outcomes as assessed by CTCAE v4.0
timeFrame: 6 weeks
measure: Adverse outcomes as assessed by CTCAE v4.0
timeFrame: 12 weeks
measure: Change in serum insulin
timeFrame: 6 weeks
measure: Change in serum insulin
timeFrame: 12 weeks
measure: Change in food diaries
timeFrame: 6 weeks
measure: Change in food diaries
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in insulin resistance
timeFrame: 6 weeks
measure: Change in insulin resistance
timeFrame: 12 weeks
measure: Change in testosterone levels
timeFrame: 6 weeks
measure: Change in testosterone levels
timeFrame: 12 weeks
measure: Change in free testosterone levels
timeFrame: 6 weeks
measure: Change in free testosterone levels
timeFrame: 12 weeks
measure: Change in dehydroepiandrosterone sulfate (DHEA-S) levels
timeFrame: 6 weeks
measure: Change in dehydroepiandrosterone sulfate (DHEA-S) levels
timeFrame: 12 weeks
measure: Change in androstenedione levels
timeFrame: 6 weeks
measure: Change in androstenedione levels
timeFrame: 12 weeks
measure: Change in sex hormone binding globulin (SHBG) levels
timeFrame: 6 weeks
measure: Change in sex hormone binding globulin (SHBG) levels
timeFrame: 12 weeks
measure: Change in 17-Hydroxyprogesterone (17-OHP) levels
timeFrame: 6 weeks
measure: Change in 17-Hydroxyprogesterone (17-OHP) levels
timeFrame: 12 weeks
measure: Change in appetite
timeFrame: 6 weeks
measure: Change in appetite
timeFrame: 12 weeks
measure: Change in markers of satiety
timeFrame: 6 weeks
measure: Change in markers of satiety
timeFrame: 12 weeks
measure: Change in markers of satiety
timeFrame: 6 weeks
measure: Change in markers of satiety
timeFrame: 12 weeks
measure: Change in markers of satiety
timeFrame: 6 weeks
measure: Change in markers of satiety
timeFrame: 12 weeks
measure: Change in markers of hunger
timeFrame: 6 weeks
measure: Change in markers of hunger
timeFrame: 12 weeks
measure: Change in fasting glucose
timeFrame: 6 weeks
measure: Change in fasting glucose
timeFrame: 12 weeks
measure: Change in HbA1c
timeFrame: 6 weeks
measure: Change in HbA1c
timeFrame: 12 weeks
measure: Change in lipids
timeFrame: 6 weeks
measure: Change in lipids
timeFrame: 12 weeks
measure: Change in lipids
timeFrame: 6 weeks
measure: Change in lipids
timeFrame: 12 weeks
measure: Change in lipids
timeFrame: 6 weeks
measure: Change in lipids
timeFrame: 12 weeks
measure: Change in lipids
timeFrame: 6 weeks
measure: Change in lipids
timeFrame: 12 weeks
measure: Change in body weight
timeFrame: 6 weeks
measure: Change in body weight
timeFrame: 12 weeks
measure: Change in body mass index
timeFrame: 6 weeks
measure: Change in body mass index
timeFrame: 12 weeks
measure: Change in anthropometric measurements (waist circumference)
timeFrame: 6 weeks
measure: Change in anthropometric measurements (waist circumference)
timeFrame: 12 weeks
measure: Change in anthropometric measurements (waist-hip ratio)
timeFrame: 6 weeks
measure: Change in anthropometric measurements (waist-hip ratio)
timeFrame: 12 weeks
measure: Change in dietary intake
timeFrame: 6 weeks
measure: Change in dietary intake
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Robert Graves Institute of Endocrinology, Tallaght University Hospital
state: Leinster
Study officials:
affiliation: Robert Graves Institute of Endocrinology, Tallaght University Hospital
name: Lucy-Ann Behan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Dublin, Trinity College
name: Sinead Duggan, R.D. PhD
role: STUDY_DIRECTOR
References:
citation: Asemi Z, Samimi M, Taghizadeh M, Esmaillzadeh A. Effects of Ramadan Fasting on Glucose Homeostasis, Lipid Profiles, Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome in Kashan, Iran. Arch Iran Med. 2015 Dec;18(12):806-10.
citation: Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018 Aug;110(3):364-379. doi: 10.1016/j.fertnstert.2018.05.004. Epub 2018 Jul 19.
citation: Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG 3rd, Leeuwenburgh C, Mattson MP. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018 Feb;26(2):254-268. doi: 10.1002/oby.22065. Epub 2017 Oct 31.
citation: 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.
citation: de Cabo R, Mattson MP. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med. 2019 Dec 26;381(26):2541-2551. doi: 10.1056/NEJMra1905136. No abstract available.
citation: Albosta M, Bakke J. Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians. Clin Diabetes Endocrinol. 2021 Feb 3;7(1):3. doi: 10.1186/s40842-020-00116-1.
citation: Zangeneh F, Salman Yazdi R, Naghizadeh MM, Abedinia N. Effect of Ramadan Fasting on Stress Neurohormones in Women with Polycystic Ovary Syndrome. J Family Reprod Health. 2015 Jun;9(2):51-7.
citation: Pellegrini M, Cioffi I, Evangelista A, Ponzo V, Goitre I, Ciccone G, Ghigo E, Bo S. Effects of time-restricted feeding on body weight and metabolism. A systematic review and meta-analysis. Rev Endocr Metab Disord. 2020 Mar;21(1):17-33. doi: 10.1007/s11154-019-09524-w.