Clinical trial NCT03987854: The University of Michigan PCOS Intervention Using Nutritional Ketosis
Official title: The University of Michigan PCOS Intervention Using Nutritional Ketosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Polycystic Ovary Syndrome
Keywords: nutrition
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-06-17
Enrollment: 29
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will be taught how to follow a very low carbohydrate, ketogenic diet, become more physically active, and get adequate sleep. Behavioral: positive affect informational materials. They will also be taught about positive affect skills, such as gratitude, positive reappraisal, and personal strengths, in addition to information about mindfulness and mindful eating techniques.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Percent Body Weight Loss
timeFrame: 4 months
Secondary outcomes:
measure: HbA1c Change
timeFrame: 4 months
Other outcomes:
measure: Polycystic Ovary Syndrome Questionnaire (PCOSQ): Emotions
timeFrame: 4 months
measure: Polycystic Ovary Syndrome Questionnaire (PCOSQ): Body Hair
timeFrame: 4 months
measure: Polycystic Ovary Syndrome Questionnaire (PCOSQ): Weight
timeFrame: 4 months
measure: Polycystic Ovary Syndrome Questionnaire (PCOSQ): Infertility
timeFrame: 4 months
measure: Polycystic Ovary Syndrome Questionnaire (PCOSQ): Menstrual Symptoms
timeFrame: 4 months
measure: Polycystic Ovary Syndrome Questionnaire (PCOSQ): Menstrual Predictability
timeFrame: 4 months
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
References:
citation: 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.