- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03480022
Liraglutide 3mg (Saxenda) on Weight, Body Composition, Hormonal and Metabolic Parameters in Obese Women With PCOS (SAXAPCOS)
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)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
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Louisiana
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Baton Rouge, Louisiana, United States, 70817
- Woman's Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / 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
|
daily sc injection of liraglutide with final dose of 3mg daily
Other Names:
|
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
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daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absolute Body Weight (BW)
Time Frame: 32 weeks of treatment
|
Treatment impact on change in body weight after 32 weeks of treatment.
|
32 weeks of treatment
|
Free Androgen Index (FAI)
Time Frame: 32 weeks of treatment
|
Drug treatment effect on free androgen levels as calculated as FAI= total testosterone (T) concentrations divided by sex hormone binding globulin (SHBG) levels.
A higher score indicates a worse outcome (more androgenic).
|
32 weeks of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Body Mass Index (BMI)
Time Frame: 32 weeks of treatment
|
Treatment effect in reducing body mass
|
32 weeks of treatment
|
Change in Percent Body Weight
Time Frame: Change from baseline (time 0) to study end (32 weeks)
|
Treatment effect on reducing body weight expressed as percent body weight loss from baseline
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Change from baseline (time 0) to study end (32 weeks)
|
5% Weight Loss From Baseline
Time Frame: 32 weeks of treatment
|
Frequency of patients achieving 5% weight loss from baseline with treatment
|
32 weeks of treatment
|
10% Body Weight Loss From Baseline
Time Frame: 32 weeks of treatment
|
Frequency of patients with at least 10% reduction in body weight from baseline
|
32 weeks of treatment
|
Abdominal Adiposity (Waist Circumference [WC]
Time Frame: 32 weeks of treatment
|
Treatment effect on loss of WC (abdominal adiposity) with drug treatment
|
32 weeks of treatment
|
Waist-to-Hip Ratio
Time Frame: 32 weeks of treatment
|
Change in central adiposity with treatment as measured by WHR.
A reduction in ratio indicates a decrease in truncal fat.
|
32 weeks of treatment
|
Waist-to Height Ratio [WHtR])
Time Frame: 32 weeks of treatment
|
Treatment effect on loss of central adiposity as determined by WHt ratio.
The lower the ratio indicates less abdominal adiposity.
|
32 weeks of treatment
|
Total Fat Mass Evaluated by DEXA
Time Frame: 32 weeks of treatment
|
Treatment effect on reduction of fat mass (kg)
|
32 weeks of treatment
|
Total Body Fat (%) by DXA
Time Frame: 32 weeks of treatment
|
Treatment effect on reduction of percent body fat by DXA
|
32 weeks of treatment
|
Android-Gynoid Ratio (AGR) by DXA
Time Frame: 32 weeks of treatment
|
Treatment impact on AGR, measure of central adiposity, as determined by DXA.
A lower AGR indicates a reduction in central adiposity.
|
32 weeks of treatment
|
Trunk/Leg Fat Ratio (TLR) by DXA
Time Frame: 32 weeks of treatment
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Treatment impact on TLR after 32 weeks.
A reduction in TLR indicates a loss of central fat.
|
32 weeks of treatment
|
Menstrual Cycle Frequency
Time Frame: 32 weeks of treatment
|
Drug treatment impact on normalization of cycle frequency (cycle every 28-30 days).
All cycle data is expressed as number of menses annualized to one year.
|
32 weeks of treatment
|
Total Testosterone Concentrations (T)
Time Frame: 32 weeks of treatment
|
Drug treatment effect on total testosterone concentrations
|
32 weeks of treatment
|
Adrenal Dehydroepiandrosterone Sulfate (DHEAS)
Time Frame: 32 weeks of treatment
|
Treatment efficacy in reducing adrenal hyperandrogenism
|
32 weeks of treatment
|
Fasting Blood Glucose (FG)
Time Frame: 32 weeks of treatment
|
Treatment effect on fasting glucose prior to an oral glucose tolerance test (OGTT)
|
32 weeks of treatment
|
OGTT Mean Blood Glucose (MBG)
Time Frame: 32 weeks of treatment
|
Treatment effect on MBG measured during the oral glucose tolerance test.
A decrease in MBG shows improvement in glycemia.
|
32 weeks of treatment
|
Fasting Insulin Sensitivity (HOMA-IR)
Time Frame: 32 weeks of treatment
|
Treatment effect on the HOMA-IR which is an insulin resistance measured derived from fasting blood glucose and insulin .
The higher the number the more insulin resistant.
|
32 weeks of treatment
|
Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT)
Time Frame: 32 weeks of treatment
|
The SI OGTT is a measure of peripheral insulin sensitivity derived from the insulin and glucoses measured during an OGTT.
A increase in SI OGTTindicates greater insulin sensitivity
|
32 weeks of treatment
|
Corrected First Phase Insulin Secretion (IGI/HOMA-IR)
Time Frame: 32 weeks of treatment
|
Treatment effect on insulin secretion from 0 to 30 minutes after glucose load corrected for by fasting insulin sensitivity.
A higher score shows improved first phase insulin secretion in response to glucose.
|
32 weeks of treatment
|
Insulin Secretion- Insulin Sensitivity Index (Oral Disposition Index-IS-SI)
Time Frame: 32 weeks of treatment
|
Treatment effect on an estimation of Beta cell compensatory function, the IS-SI is derived by applying the concept of the disposition index to measurements obtained during the 2 hour OGTT and calculated as the index of insulin secretion factored by insulin sensitivity.
A higher score shows improved pancreatic beta cell function relative to insulin sensitivity.
|
32 weeks of treatment
|
Total Cholesterol Levels
Time Frame: 32 weeks of treatment
|
Treatment impact on improving total cholesterol levels
|
32 weeks of treatment
|
High Density Lipoprotein Cholesterol (HDL-C)
Time Frame: 32 weeks of treatment
|
Impact of treatment on HDL levels after 32 weeks of treatment
|
32 weeks of treatment
|
Triglyceride Levels (TRG)
Time Frame: 32 weeks of treatment
|
Drug effect of TRG levels after treatment
|
32 weeks of treatment
|
Triglyceride to HDL-Cholesterol Ratio (TRG/HDL-C)
Time Frame: 32 weeks of treatment
|
Treatment impact on TRG/HDL-C ratio which is a simple measure to estimate insulin action.
A decrease in ratio indicates improvement in insulin sensitivity.
|
32 weeks of treatment
|
Triglyceride and Glucose Index (TyG)
Time Frame: 32 weeks of treatment
|
Treatment impact on the TyG index which estimates insulin resistance.
A reduction in TyG indicates an improvement in insulin action.
|
32 weeks of treatment
|
Systolic Blood Pressure
Time Frame: 32 weeks of treatment
|
Treatment impact on systolic blood pressure
|
32 weeks of treatment
|
Diastolic Blood Pressure (BP)
Time Frame: 32 weeks of treatment
|
Treatment impact on reducing diastolic blood pressure
|
32 weeks of treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Peggy Dean, PharmD, Woman's Hospital Foundation IRB
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- Neoplasms
- Endocrine System Diseases
- Disease
- Ovarian Cysts
- Cysts
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Diabetes Mellitus
- Polycystic Ovary Syndrome
- Syndrome
- Prediabetic State
- Body Weight
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Incretins
- Liraglutide
Other Study ID Numbers
- U1111-1198-4126
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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