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

This study has been completed.
Sponsor:
Collaborators:
Institute of Nutraceutical and Functional Foods (INAF)
Canadian Diabetes Association
Diabete Quebec
Information provided by (Responsible Party):
Helene Jacques, Laval University
ClinicalTrials.gov Identifier:
NCT01766557
First received: October 2, 2012
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Insulin Sensitivity
Polycystic Ovarian Syndrome
Other: Semi-controlled nutritional intervention with fish protein diet
Other: Semi-controlled intervention with other animal proteins

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Assessment of Cod Protein as an Insulin-sensitizing Agent in Women With Polycystic Ovary Syndrome.

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Change in sex hormones, during intervention and from baseline to the end of each intervention period. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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).

  • Change in cycle regularity during intervention period. [ Time Frame: At weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 during the intervention ] [ Designated as safety issue: No ]
    menstrual diaries

  • Change in ovarian function during intervention period. [ Time Frame: At weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 during the intervention ] [ Designated as safety issue: No ]
    progesterone measurements


Secondary Outcome Measures:
  • Change in nutritional variables from baseline to the end of each intervention period. [ Time Frame: At baseline and at the end of the intervention period (12 weeks). ] [ Designated as safety issue: No ]
    Food frequency questionnaire

  • Change in cardiometabolic statute from baseline to the end of each intervention period [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: After each intervention period (12 weeks) ] [ Designated as safety issue: No ]
    Muscle biopsies for expression and phosphorylation of IRS-1-associated PI3-K activity, as well as Akt and aPKC activation by insulin.

  • Change in physical activity habits from baseline to the end of each intervention period. [ Time Frame: At baseline and at the end of the intervention period (12 weeks) ] [ Designated as safety issue: No ]
    Physical activity habits questionnaire

  • Change in anthropometric measurements from baseline to the end of each intervention period. [ Time Frame: At baseline and at the end of the intervention period (12 weeks) ] [ Designated as safety issue: No ]
    anthropometric measurements (body mass index, waist and hip circumferences)


Enrollment: 9
Study Start Date: August 2010
Study Completion Date: December 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Semi-controlled 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.
Other: Semi-controlled nutritional intervention with fish protein diet
After a controlled NCEP-based diet for 3 months, women are assigned to a cod fillet diet. At the end of this first 3 months experimental period, participants return to their NCEP-based diet for a wash-out period of 3 months. Then, each group receive the other diet for an additional 3 months period. The fish protein intake come from cod fillets and correspond to 50% of total protein, the remaining dietary proteins being from BPVEM (20%) and vegetable (30%). Lunches incorporating cod fillets are prepared by professional dietitians, provided two time per week, and are self-consumed. Participants make their breakfasts and dinners using foods from a pre-approved list. Alcohol is strictly prohibited during all periods.
Active Comparator: 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.
Other: Semi-controlled intervention with other animal proteins
Prior to experimental period, participants follow a controlled NCEP-based diet for 3 months. Then women are assigned to a diet containing beef, pork, veal, eggs, milk and milk products. At the end of this first 3 months experimental period, participants return to their NCEP-based diet for a wash-out period of 3 months. The two diets are isoenergetic. The protein intake from BPVEM correspond to 70% of total protein, other dietary proteins are from vegetable (30%) origin. Lunches incorporating animal proteins are prepared by professional dietitians, provided two time per week, and are self-consumed. Participants make their breakfasts and dinners using foods from a pre-approved list. The content in n-3 fatty acids is adjusted to provide equivalent amounts of n-3 fatty acids then in the cod protein diet. Alcohol is strictly prohibited during all periods.

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).

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01766557

Locations
Canada
Institute Of Nutraceuticals and Functional Foods (INAF), Laval University
Quebec, Canada, G1V 0A6
Sponsors and Collaborators
Laval University
Institute of Nutraceutical and Functional Foods (INAF)
Canadian Diabetes Association
Diabete Quebec
  More Information

No publications provided

Responsible Party: Helene Jacques, Professor, Ph.D., Dt.P., Laval University
ClinicalTrials.gov Identifier: NCT01766557     History of Changes
Other Study ID Numbers: PCOS-09-08-078
Study First Received: October 2, 2012
Last Updated: February 6, 2014
Health Authority: Canada: Canadian Institutes of Health Research
Canada: Ethics Review Committee

Keywords provided by Laval University:
Polycystic ovarian syndrome, sex hormones, ovarian function, women, fish protein, insulin sensitivity, glucose tolerance, β-cell function, inflammation

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Insulin Resistance
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014