The University of Michigan PCOS Intervention Using Nutritional Ketosis

The goal of this proposal is to pilot test our existing very-low carbohydrate diet intervention, adapted for women with PCOS.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Behavioral: diet and lifestyle program

Detailed Description

Polycystic ovary syndrome (PCOS) is a common and costly ($4.3 billion/year) endocrine disorder that significantly impairs quality of life and increases the risk of obesity and type 2 diabetes as well as hyperandrogenism, infertility, hyperlipidemia, and cardiovascular disease. Diet and lifestyle weight-loss interventions are recommended as the first-line treatment of PCOS, but experts disagree about which nutritional approach is best. A review of previous diet and lifestyle trials in PCOS did find a slight benefit of lower carbohydrate diets for weight loss, glucose control, insulin, and insulin resistance. This may be because carbohydrate intake leads to increased insulin secretion, which then stimulates ovarian androgen production and inhibits the release of fatty acids from cells, both of which worsen PCOS-related issues. Although lower carbohydrate diets may be helpful, research from other populations with or at risk of type 2 diabetes suggests that prior PCOS studies may have set insufficient carbohydrate reduction targets. The investigators propose that a very-low carbohydrate diet may be needed to especially benefit women with PCOS, as greater carbohydrate reduction should have a larger impact on androgen levels and weight loss. Thus, the goal of this proposal is to pilot test our existing very-low carbohydrate diet intervention, adapted for women with PCOS.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• We will include women in one PCOS subtype, those having these two symptoms:

  • Hyperandrogenism - (a) If not on current birth control: hyperandrogenism defined as current elevated total testosterone >= 50 ng/dL or free androgen index > 1.5 (ratio of testosterone/SHBG x 100) or severe acne or hirsutism (b) if on current birth control: history from the past 10 years of hyperandrogenism defined as past elevated total testosterone >= 50 ng/dL or free androgen index > 1.5 (ratio of testosterone/SHBG x 100) or severe acne or hirsutism
  • oligomenorrhea-anovulation defined as spontaneous intermenstrual periods of ≥ 45 days or a total of ≤ 8 menses per year.

Participants must also be:

• overweight or obese (BMI 25-50)
• be 21-40 years old
• have regular access to the internet
• be able to engage in light physical activity
• willing and able to follow the assigned intervention.

Exclusion Criteria:

• a non-English speaker
• inability to complete baseline measurements
• a substance abuse, mental health, or medical condition that would interfere with participation (such as current chemotherapy)
• pregnant or planning to get pregnant in the next 6 months
• type 1 or type 2 diabetes
• baseline aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times normal
• baseline renal disease defined as BUN > 30 mg/dL or serum creatinine >1.4 mg/dL
• baseline uncorrected thyroid disease (TSH <0.45 mIU/ML or >4.5 mIU/ML)
• breastfeeding or less than 6 months post-partum
• planned or history of weight loss surgery
• vegan or vegetarian
• currently enrolled in a weight loss program or other investigative study that might conflict with this research
• taking medications known to cause weight gain or loss
• taking hypoglycemic medications other than metformin or medications known to affect metabolism
• or patients with other etiologies of anovulation and hyperandrogenism, e.g., Cushing's disease, thyroid dysfunction, elevated prolactin levels, signs of congenital adrenal hyperplasia, organic intra cranial lesion such as a pituitary tumor, or suspected adrenal or ovarian tumor secreting androgens.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: complete diet and lifestyle program	Behavioral: diet and lifestyle program; Participants will be taught how to follow a very low carbohydrate, ketogenic diet, become more physically active, and get adequate sleep. They will also be taught taught about positive affect skills (such as gratitude, positive reappraisal, and personal strengths) and mindfulness (general mindfulness and mindful eating).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Body Weight Loss	Mean percent body weight loss was defined as: (weight at 4 months - baseline weight) / (baseline weight) *100.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c Change	percentage of glycosylated hemoglobin	4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polycystic Ovary Syndrome Questionnaire (PCOSQ): Emotions	Scale measures health-related quality-of-life for Women with PCOS with five domains: emotions, body hair, weight, infertility, and menstrual problems. It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.	4 months
Polycystic Ovary Syndrome Questionnaire (PCOSQ): Body Hair	Scale measures health-related quality-of-life for Women with PCOS with five domains: emotions, body hair, weight, infertility, and menstrual problems. It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.	4 months
Polycystic Ovary Syndrome Questionnaire (PCOSQ): Weight	Scale measures health-related quality-of-life for Women with PCOS with five domains: emotions, body hair, weight, infertility, and menstrual problems. It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.	4 months
Polycystic Ovary Syndrome Questionnaire (PCOSQ): Infertility	Scale measures health-related quality-of-life for Women with PCOS with five domains: emotions, body hair, weight, infertility, and menstrual problems. It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.	4 months
Polycystic Ovary Syndrome Questionnaire (PCOSQ): Menstrual Symptoms	Scale measures health-related quality-of-life for Women with PCOS with five domains: emotions, body hair, weight, infertility, and menstrual problems. It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.	4 months
Polycystic Ovary Syndrome Questionnaire (PCOSQ): Menstrual Predictability	Scale measures health-related quality-of-life for Women with PCOS with five domains: emotions, body hair, weight, infertility, and menstrual problems. It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.	4 months

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Missel AL, O'Brien AV, Maser H, Kanwal A, Bayandorian H, Martin S, Carrigan P, McNamee R, Daubenmier J, Isaman DJM, Padmanabhan V, Smith YR, Aikens JE, Saslow LR. Impact of an online multicomponent very-low-carbohydrate program in women with polycystic ovary syndrome: a pilot study. F S Rep. 2021 Sep 4;2(4):386-395. doi: 10.1016/j.xfre.2021.08.008. eCollection 2021 Dec.

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2019
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 14, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 22, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: nutrition
• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome
• Other Study ID Numbers: HUM00113697; P30DK092926 (U.S. NIH Grant/Contract); K01DK107456 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No