Time-restricted Eating to Improve Metabolic Abnormalities in Polycystic Ovarian Syndrome

Insulin Resistance Clinical Trial

— TimeMAP  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05126199
• Other study ID #: TimeMAP
• Status: Recruiting
• Phase: N/A
• Start date: May 5, 2021
• Est. completion date: January 31, 2023

Study information

• Verified date: September 2022
• Source: Tallaght University Hospital
• Contact: Ruairí Floyd, BSc BMBS
• Phone: (01) 414 2000
• Email: floydr[@]tcd.ie
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperinsulinemia
• Hyperinsulinism
• Insulin Resistance
• PCOS
• Polycystic Ovary Syndrome

Intervention

Other:
• Time restricted eating
Following a 3 day baseline dietary assessment using the Nutritics 'app', patients will immediately commence time-restricted eating on a 18:6 basis (18 hours fasting, 6 hours eating window) for 12 weeks. Participants will consume all their meals within a daily 6-hour period of their choosing, and this may change according to patient's lifestyle and preference to reflect a real-world situation. Participants may eat ad libitum / according to appetite during the eating period. Participants will fast for 18 hours per day, consuming only plain water, unflavoured/unsweetened sparkling water, black breakfast tea or black coffee. Alcohol must not be consumed during fasting periods Dietary intake will again be measured using the Nutritics 'app' midpoint through the 12-week period (week 6 +/- 1 week) and in the last week of the intervention (week 11/12).
• Normal ad libitum diet
Following a 3-day baseline dietary assessment using the Nutritics 'app', participants with be directed to continue with their usual dietary intake without any time-related restrictions for 12 weeks. There will be no defined eating window and fasting or restrictions regarding types of food or drink consumed. Dietary intake will again be measured using the Nutritics 'app' midpoint through the 12-week period (week 6 +/- 1 week) and in the last week of the intervention (week 11/12).

Locations

Country	Name	City	State
Ireland	Robert Graves Institute of Endocrinology, Tallaght University Hospital	Dublin	Leinster

Sponsors (2)

Lead Sponsor	Collaborator
Ruairí Floyd	Tallaght University Hospital

Country where clinical trial is conducted

Ireland, 

References & Publications (8)

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. Review. — View 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. Review. — View 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. doi: 0151812/AIM.003. — View 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. Review. Erratum in: N Engl J Med. 2020 Jan 16;382(3):298. N Engl J Med. 2020 Mar 5;382(10):978. — View 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. — View 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. Erratum in: Rev Endocr Metab Disord. 2020 Feb 18;:. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Drop-out rate	Assessing intervention feasibility	6 weeks
Primary	Drop-out rate	Assessing intervention feasibility	12 weeks
Primary	Adverse outcomes as assessed by CTCAE v4.0	Assessing intervention feasibility	6 weeks
Primary	Adverse outcomes as assessed by CTCAE v4.0	Assessing intervention feasibility	12 weeks
Primary	Change in serum insulin	Measured with serum insulin levels to assess effects	6 weeks
Primary	Change in serum insulin	Measured with serum insulin levels to assess effects	12 weeks
Primary	Change in food diaries	Assessment of change of eating behaviours	6 weeks
Primary	Change in food diaries	Assessment of change of eating behaviours	12 weeks
Secondary	Change in insulin resistance	Assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and other ratio calculations measuring insulin resistance	6 weeks
Secondary	Change in insulin resistance	Assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and other ratio calculations measuring insulin resistance	12 weeks
Secondary	Change in testosterone levels	Assessed by plasma testosterone	6 weeks
Secondary	Change in testosterone levels	Assessed by plasma testosterone	12 weeks
Secondary	Change in free testosterone levels	Assessed by plasma free testosterone	6 weeks
Secondary	Change in free testosterone levels	Assessed by plasma free testosterone	12 weeks
Secondary	Change in dehydroepiandrosterone sulfate (DHEA-S) levels	Assessed by plasma dehydroepiandrosterone sulfate (DHEA-S)	6 weeks
Secondary	Change in dehydroepiandrosterone sulfate (DHEA-S) levels	Assessed by plasma dehydroepiandrosterone sulfate (DHEA-S)	12 weeks
Secondary	Change in androstenedione levels	Assessed by plasma androstenedione	6 weeks
Secondary	Change in androstenedione levels	Assessed by plasma androstenedione	12 weeks
Secondary	Change in sex hormone binding globulin (SHBG) levels	Assessed by plasma sex hormone binding globulin (SHBG)	6 weeks
Secondary	Change in sex hormone binding globulin (SHBG) levels	Assessed by plasma sex hormone binding globulin (SHBG))	12 weeks
Secondary	Change in 17-Hydroxyprogesterone (17-OHP) levels	Assessed by 17-Hydroxyprogesterone (17-OHP)	6 weeks
Secondary	Change in 17-Hydroxyprogesterone (17-OHP) levels	Assessed by 17-Hydroxyprogesterone (17-OHP)	12 weeks
Secondary	Change in appetite	Measured by a validated 10-point visual analogue scale on a scale of 1-10, 1 being not hungry at all and 10 being very hungry	6 weeks
Secondary	Change in appetite	Measured by a validated 10-point visual analogue scale on a scale of 1-10, 1 being not hungry at all and 10 being very hungry	12 weeks
Secondary	Change in markers of satiety	Assess by plasma GLP-1	6 weeks
Secondary	Change in markers of satiety	Assess by plasma GLP-1	12 weeks
Secondary	Change in markers of satiety	Assess by plasma PYY	6 weeks
Secondary	Change in markers of satiety	Assess by plasma PYY	12 weeks
Secondary	Change in markers of satiety	Assess by plasma oxyntomodulin	6 weeks
Secondary	Change in markers of satiety	Assess by plasma oxyntomodulin	12 weeks
Secondary	Change in markers of hunger	Assess by plasma ghrelin	6 weeks
Secondary	Change in markers of hunger	Assess by plasma ghrelin	12 weeks
Secondary	Change in fasting glucose	Assessed in serum glucose measurements	6 weeks
Secondary	Change in fasting glucose	Assessed in serum glucose measurements	12 weeks
Secondary	Change in HbA1c	Assessed in serum HbA1c measurements	6 weeks
Secondary	Change in HbA1c	Assessed in serum HbA1c measurements	12 weeks
Secondary	Change in lipids	Assessed by Lipid profile	6 weeks
Secondary	Change in lipids	Assessed by Lipid profile	12 weeks
Secondary	Change in lipids	Assessed by Lipoprotein lipid A levels	6 weeks
Secondary	Change in lipids	Assessed by Lipoprotein lipid A levels	12 weeks
Secondary	Change in lipids	Assessed by Apolipoprotein A1 levels	6 weeks
Secondary	Change in lipids	Assessed by Apolipoprotein A1 levels	12 weeks
Secondary	Change in lipids	Assessed by Apolipoprotein B levels	6 weeks
Secondary	Change in lipids	Assessed by Apolipoprotein B levels	12 weeks
Secondary	Change in body weight	Body weight (kg)	6 weeks
Secondary	Change in body weight	Body weight (kg)	12 weeks
Secondary	Change in body mass index	BMI (kg/m2)	6 weeks
Secondary	Change in body mass index	BMI (kg/m2)	12 weeks
Secondary	Change in anthropometric measurements (waist circumference)	Waist circumference (cm)	6 weeks
Secondary	Change in anthropometric measurements (waist circumference)	Waist circumference (cm)	12 weeks
Secondary	Change in anthropometric measurements (waist-hip ratio)	Waist-hip ratio	6 weeks
Secondary	Change in anthropometric measurements (waist-hip ratio)	Waist-hip ratio	12 weeks
Secondary	Change in dietary intake	Assessed using interval dietary assessments with Nutritics 'app'	6 weeks
Secondary	Change in dietary intake	Assessed using interval dietary assessments with Nutritics 'app'	12 weeks

External Links

•   BDA The Association of UK Dieticians - Polycystic Ovary Syndrome (PCOS) Food Fact Sheet
•   The Irish Nutrition and Dietetic Institute - Polycystic Ovary Syndrome (PCOS)