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Liraglutide 3mg (Saxenda) on Weight, Body Composition, Hormonal and Metabolic Parameters in Obese Women With PCOS (SAXAPCOS)

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ClinicalTrials.gov Identifier: NCT03480022
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Karen Elkind-Hirsch, Woman's

Brief Summary:
There is a growing need to develop pharmacologic interventions to improve metabolic function in women with polycystic ovary syndrome (PCOS). Given that PCOS is a frequent condition and weight loss is essential but difficult to achieve, it is important to study if the effect on body weight reported in other studies can be confirmed in a selected population of hyperandrogenic patients, especially with medications currently approved for weight reduction. High dose liraglutide alone results in significant weight reduction in obese women without PCOS. There is limited data on weight loss with high dose liraglutide in non-diabetic females with PCOS treated with this agent . Studies on the effect of anti-obesity medication combined with lifestyle changes on body weight and composition and androgen excess in obese women diagnosed with PCOS are lacking. The investigators aim to elucidate the most efficacious weight reduction regime in obese PCOS women. The investigators further hope to determine which treatment(s) addressing the multifaceted disturbances of this disorder in patients with PCOS and obesity emerges as the preferable therapy.

Condition or disease Intervention/treatment Phase
Pre Diabetes Polycystic Ovary Syndrome Obesity Android Drug: Liraglutide Pen Injector [Saxenda] Drug: Placebo Liraglutide Pen Injector Phase 3

Detailed Description:

The drug, liraglutide 3.0 mg was approved for chronic weight management in management in obese adults with an initial BMI of 30 kg/m2 or greater or in overweight adults BMI of 27 kg/m2 or greater with at least one weight-related co-morbid condition as an adjunct to a reduced-calorie diet and increased physical activity. Liraglutide is an acylated human glucagon-like peptide -1 (GLP-1) analog that binds to and activates the GLP-1 receptor. It lowers body weight through decreased caloric intake while stimulating insulin secretion and reducing glucagon via a glucose-dependent mechanism. For obesity management, patients may lose weight with GLP-1 receptor agonists due to other unique actions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can slow gastric emptying and increase satiety. While predictors of weight loss success for the general population are available (protein intake, weight loss medications), predictors of weight loss success may differ between normal and hyperandrogenic women. Glucagon-like peptide 1 agonists are linked with dose dependent weight lowering potential in different obesity related populations. The weight loss effects of GLP-1RAs previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to patients with PCOS.

Given this lack of information, the aim of the present study was to investigate the effects of liraglutide 3mg vs. placebo on body composition as well as hormonal and metabolic features in non-diabetic obese women with PCOS.The non-diabetic obese female with PCOS offers a unique model to study the relationship between insulin resistance and adiposity. The investigators propose a double-blind, placebo-controlled 30-week trial designed to directly examine the therapeutic effects of liraglutide 3 mg (LIRA 3 mg) compared to placebo on body weight, hormonal and cardiometabolic parameters in obese non-diabetic women with PCOS. All patients will receive diet and lifestyle counseling, including advice on exercise commencing during the lead-in period and continuing throughout the study. In this study, the investigators will examine the efficacy of LIRA 3mg on body weight and body composition, reproductive function metabolic parameters and cardiovascular risk factors in a well-defined group of pre-menopausal obese non-diabetic women with hyperandrogenism, focusing on the relationship to obesity and insulin resistance.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double- Blind 2:1 Drug: Placebo
Primary Purpose: Treatment
Official Title: A Randomized Placebo-controlled Double Blind Trial of Liraglutide 3 mg [Saxenda] on Weight, Body Composition, Hormonal and Metabolic Parameters in Obese Women With Polycystic Ovary Syndrome (PCOS)
Actual Study Start Date : September 26, 2018
Estimated Primary Completion Date : October 8, 2020
Estimated Study Completion Date : November 15, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Experimental: Liraglutide Pen Injector (Saxenda)
Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily
Drug: Liraglutide Pen Injector [Saxenda]
daily sc injection of liraglutide with final dose of 3mg daily
Other Names:
  • Liraglutide 3mg
  • Saxenda

Placebo Comparator: Placebo liraglutide pen injector
Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily
Drug: Placebo Liraglutide Pen Injector
daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo
Other Names:
  • Placebo Saxenda
  • Placebo liraglutide 3 mg




Primary Outcome Measures :
  1. Body weight (BW) [ Time Frame: Baseline to week 30 ]
    Treatment impact on percent change in BW and participants reaching >5% reduction

  2. Free androgen index (FAI =total testosterone (T)/sex hormone binding globulin (SHBG) levels] ) [ Time Frame: Baseline to week 30 ]
    Treatment impact on reduction of FAI


Secondary Outcome Measures :
  1. Body mass index (BMI) [ Time Frame: Baseline to week 30 ]
    Treatment effect in reducing body mass

  2. Frequency of patients achieving a body weight reduction of at least 10% [ Time Frame: Baseline to week 30 ]
    Treatment effect on weight loss

  3. Abdominal adiposity (waist circumference [WC] [ Time Frame: Baseline to week 30 ]
    Treatment effect on loss of abdominal adiposity

  4. Central adiposity ( waist-to height ratio [WHtR]) [ Time Frame: Baseline to week 30 ]
    Treatment effect on loss of central adiposity

  5. Distribution of fat evaluated by DEXA [ Time Frame: Baseline to week 30 ]
    Treatment effect on reduction central fat distribution

  6. Total fat mass evaluated by DEXA [ Time Frame: Baseline to week 30 ]
    Treatment effect on reduction of fat mass

  7. Adrenal dehydroepiandrosterone sulfate (DHEAS) [ Time Frame: Baseline to week 30 ]
    Treatment efficacy in reducing adrenal hyperandrogenism

  8. Menstruation frequency [ Time Frame: Baseline to week 30 ]
    Treatment impact on normalization of cycle frequency

  9. Change in glycemic responses from a glucose challenge [ Time Frame: Baseline to week 30 ]
    Treatment effect on fasting and 2 hour glucose during an oral glucose tolerance test (OGTT)

  10. Surrogate measures of insulin sensitivity [ Time Frame: Baseline to week 30 ]
    Treatment effect on insulin sensitivity indices determined from fasting and OGTT measures

  11. Pancreatic beta cell compensatory function measures [ Time Frame: Baseline to week 30 ]
    Treatment effect on improving first phase insulin secretion

  12. Oral disposition (insulin secretion-sensitivity index) [ Time Frame: Baseline to week 30 ]
    Treatment effect on improving insulin action modeled from a 2 hour OGTT

  13. Lipid fractions (total cholesterol [CHOL], HDL-CHOL, LDL-CHOL and triglyceride [TRG] levels [ Time Frame: Baseline to week 30 ]
    Treatment impact on improving cardiometabolic markers

  14. Systolic and diastolic blood pressure (BP) [ Time Frame: Baseline to week 30 ]
    Treatment impact on reducing blood pressure


Other Outcome Measures:
  1. Safety laboratory measures (creatinine plus estimated glomerular filtration rate [eGFR]) [ Time Frame: Baseline to week 30 ]
    Determine if treatment has any adverse impact on renal function as evaluated by blood levels of creatinine and estimated creatinine clearance (eGFR)

  2. Safety laboratory measures ( aspartate transaminase [AST) levels [ Time Frame: Baseline to week 30 ]
    Determine if treatment has any adverse impact on liver function as evaluated by AST enzyme concentration

  3. Safety laboratory measures ( alanine transaminase [ALT]) levels [ Time Frame: Baseline to week 30 ]

    Determine if treatment has any adverse impact on liver function as evaluated by

    ALT enzyme concentrations


  4. Pregnancy tests (laboratory measures and home tests) [ Time Frame: Baseline to week 30 ]
    Confirm patients are not pregnant while under treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Patients must be female to have the disorder being studied since it involved the female reproductive system
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female gender
  • 18-45 years of age
  • BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with one or more obesity-associated co-morbid conditions (e.g. hypertension, and dyslipidemia)
  • PCOS- NIH criteria hyperandrogenism and irregular menstrual cyclicity
  • Non-diabetic as determined by a 75 gram oral glucose tolerance test (OGTT) and hemoglobin A1C. Non-diabetic is inclusive of women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT). Participants with diabetes will be excluded
  • Willing to use effective contraception consistently during therapy which is defined as:

    • an intrauterine device, tubal sterilization, or male partner vasectomy, or
    • combination of two barrier methods with one being male condom.
  • Written consent for participation in the study

Exclusion Criteria:

  • Presence of significant systemic disease, cerebrovascular disease, clinically significant cardiac abnormalities or heart problems including congestive heart failure, unstable angina or acute myocardial infarction, current infectious liver disease, acute stroke or transient ischemic attacks, history of pancreatitis, or diabetes mellitus (Type 1 or 2)
  • Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or significant abnormal liver function tests defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
  • Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or eGFR <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease.
  • Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or clinically significant elevations in prolactin levels. The clinical significance of prolactin levels will be determined by the treating physician
  • Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %)
  • Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)
  • Use of hormonal medications, the use of medications that cause clinically significant weight gain or loss (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, hormonal contraceptives, GnRH analogues, glucocorticoids, anabolic steroids, C-19 progestins) including herbal medicines for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) for at least 4 weeks
  • Prior history of a malignant disease requiring chemotherapy
  • Family or personal history of familial medullary thyroid carcinoma or multiple endocrine neoplasia type 2
  • Known hypersensitivity or contraindications to use GLP1 receptor agonists
  • Use of metformin, thiazolidinediones, GLP-1 receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium/glucose co-transporter 2 (SGLT2) inhibitors or weight loss medications (prescription or OTC) stopped for at least 4 weeks
  • Prior use of medication to treat diabetes except gestational diabetes
  • Eating disorders (anorexia, bulimia) or gastrointestinal disorders
  • Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy in next 15 months, breastfeeding, or known pregnancy in last three months
  • Active or prior history of substance abuse (smoke or tobacco use within past 6 months) or significant intake of alcohol
  • Previous bariatric surgery or device intervention for obesity
  • Patient not willing to use barrier contraception during study period (unless sterilized or have an IUD)
  • History of major depressive or other severe psychiatric disorders
  • Inability or refusal to comply with protocol
  • Currently participating or having participated in an experimental drug study in previous three months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480022


Contacts
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Contact: Karen Elkind-Hirsch, PhD 225-231-5278 karen.elkind-hirsch@womans.org
Contact: Donna Shaler, BS 225-231-5268 donna.shaler@womans.org

Locations
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United States, Louisiana
Woman's Hospital Recruiting
Baton Rouge, Louisiana, United States, 70817
Contact: Karen Elkind-Hirsch, PhD.    225-231-5278      
Contact: Ericka Seidemann, MS    225-231-5275    ericka.seidemann@womans.org   
Principal Investigator: Karen Elkind-Hirsch, Ph.D.         
Sub-Investigator: Renee Harris, M.D.         
Sub-Investigator: Drake Belanger, MD         
Sub-Investigator: Neil Chappell, M.D.         
Sponsors and Collaborators
Woman's
Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Karen Elkind-Hirsch, Woman's:
Informed Consent Form  [PDF] September 28, 2018


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Responsible Party: Karen Elkind-Hirsch, Scientific Director of Research, Woman's
ClinicalTrials.gov Identifier: NCT03480022    
Other Study ID Numbers: U1111-1198-4126
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karen Elkind-Hirsch, Woman's:
prediabetes
PCOS
GLP-1 agonist
weight loss
Additional relevant MeSH terms:
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Polycystic Ovary Syndrome
Prediabetic State
Syndrome
Body Weight
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Signs and Symptoms
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists