Assessment of Cod Protein as an Insulin-sensitizing Agent in Women With Polycystic Ovary Syndrome.

Not Applicable

Completed

• Conditions: Insulin Sensitivity; Polycystic Ovarian Syndrome
• Interventions: Other: Semi-controlled nutritional intervention with fish protein diet; Other: Semi-controlled intervention with other animal proteins

• Registration Number: NCT01766557
• Lead Sponsor: Laval University

Brief Summary

The objective of our study is to determine the effects of fish protein on insulin sensitivity in PCOS women with insulin resistance, and its mechanism of action on glucose and endocrine metabolism. Our working hypothesis is that dietary fish protein improves insulin sensitivity, glucose tolerance, and related plasma endocrine and lipid abnormalities in PCOS women by restoring secretory β-cell function and insulin signaling to the PI 3-kinase activity/Akt pathway. We further hypothesize that fish protein will improve cycle regularity and ovarian function.

Detailed Description

Women with polycystic ovary syndrome are at high risk of developing diabetes. Apart from a primary ovarian defect, up to 10% and 40-50% of those women develop diabetes and insulin resistance (IR) respectively. IR and associated hyperinsulinemia are recognized as important pathogenic factors in determining diabetes in the majority of PCOS women, particularly when obesity is present. Treating IR might reduce the risk of diabetes and improve ovulation and fertility in PCOS women. We recently found that obese, IR men and women consuming a cod protein diet showed a 30% improvement in insulin sensitivity compared with other animal proteins, and also a 24% decrease in high-sensitive C-reactive protein plasma concentration. Therefore, dietary fish protein could represent a natural, safe and practical means to improve insulin sensitivity in PCOS women with IR, and a new non-pharmaceutical approach for the treatment of the multiple endocrine and metabolic abnormalities of PCOS women (see outcome measures for a more extensive description).

Study Timeline

• Study Start: 2010-08
• Study First Submitted: 2012-10-02
• Primary Completion: 2012-12
• Study First Submitted QC: 2013-01-09
• Study First Posted: 2013-01-11
• Study Completion: 2013-12
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-06
• Last Update Posted: 2014-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 9

Inclusion Criteria

• women
• 18 to 45 years old
• having polycystic ovarian syndrome
• overweight (BMI>27)
• insulin resistance based on fasting insulin levels in the upper 95th percentile (>90pmol/L)
• non-diabetic

Exclusion Criteria

• diabetes
• hysterectomy
• abnormal endometrial biopsy if abnormal bleeding in the last 6 months
• clinical evidence of Cushing's syndrome
• congenital adrenal hyperplasia (17-OH progesterone>10nmol/l)
• excessive androgens suspicious of a tumour
• prolactins levels >50μg/l
• previous breast, uterus, ovary or liver neoplasia
• use of medication known to affect glucose and lipid metabolisms (e.g. steroid hormones, oral contraceptives, ß-blockers, glitazones, statins, insulin)
• depo-medroxyprogesterone acetate injection in the last year
• important weight loss or weight gain within the last 6 months
• chronic, metabolic (except well controlled chronic hypothyroidism) or acute disease or major surgery within the last 3 months
• dietary incompatibility with calcium supplementation and/or fish consumption (allergy, intolerance, dislike)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Semi-controlled intervention with fish protein diet	Semi-controlled nutritional intervention with fish protein diet	Women with polycystic ovarian syndrome who are assigned to a 12 weeks experimental diet containing cod as the protein source.
Semi-controlled intervention with other animal proteins	Semi-controlled intervention with other animal proteins	Women with polycystic ovarian syndrome who are assigned to a 12 week experimental diet containing beef, pork, veal, eggs and milk products (BPVEM) as protein sources.

Primary Outcome Measures

Name	Time	Method
Change in ovarian function during intervention period.	At weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 during the intervention	progesterone measurements
Change in cycle regularity during intervention period.	At weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 during the intervention	menstrual diaries
Change in sex hormones, during intervention and from baseline to the end of each intervention period.	At baseline, after the wash-out period, at the end of each intervention period (12 weeks), and at weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 during the intervention.	Detailed plasma androgen profile including active androgens (testosterone and dihydrotestosterone), adrenal androgens (androstenedione, dehydroepiandrosterone and its sulphate), major glucuronide-conjugated androgen metabolites, plasma levels of the sex hormone transport protein Sex Hormone-Binding Globulin (SHBG).

Secondary Outcome Measures

Name	Time	Method
Change in anthropometric measurements from baseline to the end of each intervention period.	At baseline and at the end of the intervention period (12 weeks)	anthropometric measurements (body mass index, waist and hip circumferences)
Change in nutritional variables from baseline to the end of each intervention period.	At baseline and at the end of the intervention period (12 weeks).	Food frequency questionnaire
Change in physical activity habits from baseline to the end of each intervention period.	At baseline and at the end of the intervention period (12 weeks)	Physical activity habits questionnaire
Change in cardiometabolic statute from baseline to the end of each intervention period	At baseline (at the beginning of the intervention), after the 12 weeks wash-out period, and at the end of each intervention period (12 weeks each)	Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, glucose and insulin concentrations during a 180-min euglycemic-hyperinsulinemic clamp, GDR, MI, β-cell function, systolic and diastolic blood pressure, glucose and insulin concentrations during a 120-min oral glucose tolerance test, plasma C-peptide concentration, apolipoprotein apoA-1, A-2 and B plasma concentrations, hsCRP, MCP-1, IL-1β, IL-6 and adiponectin concentrations.
Muscle insulin signaling	After each intervention period (12 weeks)	Muscle biopsies for expression and phosphorylation of IRS-1-associated PI3-K activity, as well as Akt and aPKC activation by insulin.

Trial Locations

Locations (1)

Institute Of Nutraceuticals and Functional Foods (INAF), Laval University; 🇨🇦 Quebec, Canada