Time Restricted Eating for the Treatment of PCOS

Study Overview
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Brief Summary
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Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility among young women. This syndrome is a reproductive and endocrinological disorder that affects up to 18% of reproductive-aged women. To date, the only strategy shown to reverse PCOS is sustained weight loss of 5-10%. At present, daily calorie restriction (CR) is the main diet prescribed to patients with PCOS for weight loss. However, some women find it difficult to adhere to CR because calorie intake must be vigilantly monitored every day. Considering these problems with CR, another approach that limits timing of food intake, instead of number of calories consumed, has been developed. This diet is called time restricted eating (TRE) and involves confining the period of food intake to 6-8 h per day. TRE allows individuals to self-select foods and eat ad libitum during a large part of the day, which greatly increases compliance to these protocols. Recent findings show that TRE significantly reduces body weight, insulin resistance, and inflammation in adults with obesity. However, no randomized controlled trials have studied the role of TRE in treating PCOS. Accordingly, this study will compare the effects of TRE vs CR in females with PCOS over 6 months on body weight, androgen markers, inflammatory markers and insulin sensitivity. Methods: A 6-month randomized, controlled, parallel-arm trial will be implemented. Females with obesity and PCOS will be randomized to 1 of 3 groups: (1) 6-h TRE (ad libitum food intake from 1-7 pm, fasting from 7pm-1pm); (2) CR (25% energy restriction daily); or (3) control group (ad libitum intake with no meal timing restrictions).

Official Title
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Time Restricted Eating for the Treatment of Polycystic Ovarian Syndrome (PCOS)

Conditions
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Polycystic Ovary Syndrome, Obesity

Intervention / Treatment
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* Other: 6-h Time restricted eating (TRE)
* Other: Calorie restriction (CR)
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosed with PCOS based on the Rotterdam criteria in which two of three of the following criteria are present: (i) androgen excess skin manifestations (hirsutism, acne, and seborrhea) and/or hyperandrogenemia (total testosterone >55 pg/ml, free testosterone >9.4 pg/ml, androstenedione >2.1 ng/ml or DHEA-S >340 ug/dl); (ii) polycystic ovarian morphology on ultrasound; and (iii) chronic oligo-amenorrhea (intermenstrual intervals >35 days or 7 periods/year) BMI between 25-50 kg/m2 Age between 18-40 years Exclusion criteria: Postmenopausal (absence of menses for >2 y) Diagnosed type 1 diabetes or type 2 diabetes Have a history of eating disorders (anorexia, bulimia, or binge eating disorder) Are not weight stable for 3 months prior to the beginning of the study (weight gain or loss > 4 kg) Are taking drugs that affect study outcomes, such as oral contraceptives, weight loss, insulin-sensitizing agents, androgen antagonists, anti-seizure, or antipsychotic medication (within 2 months of starting study) Are athletes or those engaging in >1 hour of high-intensity training on more than 5 days/week Are active smokers (within 3 months of starting the study) Do not have a Wi-Fi connection at home (needed for zoom calls) Pregnant or trying to become pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6-hour Time restricted eating (TRE)<br>Ad libitum food intake from 1-7 pm every day Fasting from 7-1 pm every day (18-h fast) | Other: 6-h Time restricted eating (TRE)<br>* Ad libitum food intake from 1-7 pm every day Fasting from 7-1 pm every day (18-h fast)<br>|
| Experimental: Calorie restriction (CR)<br>25% energy restriction every day | Other: Calorie restriction (CR)<br>* 25% energy restriction every day<br>|
| Experimental: Control<br>Usual diet | Other: Control<br>* Usual diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Measured by an electronic scale | Measured at month 0 and 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fat mass, lean mass, visceral fat mass | Measured by DXA | Measured at month 0 and 6 | 
| Change in bone mineral density | Measured by DXA | Measured at month 0 and 6 | 
| Change in waist circumference | Measured by a measuring tape | Measured at month 0 and 6 | 
| Change in Insulin sensitivity | Measured by oral glucose tolerance test (OGTT) | Measured at month 0 and 6 | 
| Change in Fasting glucose | Measured by a commercial lab (Medstar, IL) | Measured at month 0 and 6 | 
| Change in Fasting insulin | Measured by a commercial lab (Medstar, IL) | Measured at month 0 and 6 | 
| Change in HbA1c | Measured by a commercial lab (Medstar, IL) | Measured at month 0 and 6 | 
| Change in Blood pressure | Measured by a blood pressure cuff | Measured at month 0 and 6 | 
| Change in heart rate | Measured by a blood pressure cuff | Measured at month 0 and 6 | 
| Change in Plasma lipids (LDL cholesterol, HDL cholesterol, triglycerides) | Measured by a commercial lab (Medstar, IL) | Measured at month 0 and 6 | 
| Change in inflammatory markers (TNF-apha, IL-6, IL-10, IL-B, hs-CRP) | Measured by ELISA | Measured at month 0 and 6 | 
| Change in oxidative stress (8-isoprostane) | Measured by ELISA | Measured at month 0 and 6 | 
| Change in reproductive hormones (testosterone, DHEA, SHBG, androstenedione) | Measured by ELISA | Measured at month 0 and 6 | 
| Change in energy and nutrient intake | Measured by 7-day food record | Measured at month 0 and 6 | 
| Change in physical activity (steps/d) | Measured by pedometer | Measured at month 0 and 6 | 
| Change in mood | Measured by 36-Item Short Form Survey (SF-36), total score 0-100. Higher scores mean worse outcome. | Measured at month 0 and 6 | 
| Change in appetite | Measured by Visual analog scale (VAS). Scored from 0-100. Higher score means higher appetite. | Measured at month 0 and 6 |