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 : Completed
First Posted : March 27, 2018
Results First Posted : June 7, 2021
Last Update Posted : June 7, 2021
|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|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||88 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double- Blind 2:1 Drug: Placebo|
|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|
|Actual Primary Completion Date :||February 22, 2021|
|Actual Study Completion Date :||May 19, 2021|
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
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
- Absolute Body Weight (BW) [ Time Frame: 32 weeks of treatment ]Treatment impact on change in body weight after 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).
- Body Mass Index (BMI) [ Time Frame: 32 weeks of treatment ]Treatment effect in reducing body mass
- 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
- 5% Weight Loss From Baseline [ Time Frame: 32 weeks of treatment ]Frequency of patients achieving 5% weight loss from baseline with 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
- Abdominal Adiposity (Waist Circumference [WC] [ Time Frame: 32 weeks of treatment ]Treatment effect on loss of WC (abdominal adiposity) with drug 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.
- 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.
- Total Fat Mass Evaluated by DEXA [ Time Frame: 32 weeks of treatment ]Treatment effect on reduction of fat mass (kg)
- Total Body Fat (%) by DXA [ Time Frame: 32 weeks of treatment ]Treatment effect on reduction of percent body fat by DXA
- 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.
- Trunk/Leg Fat Ratio (TLR) by DXA [ Time Frame: 32 weeks of treatment ]Treatment impact on TLR after 32 weeks. A reduction in TLR indicates a loss of central fat.
- 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.
- Total Testosterone Concentrations (T) [ Time Frame: 32 weeks of treatment ]Drug treatment effect on total testosterone concentrations
- Adrenal Dehydroepiandrosterone Sulfate (DHEAS) [ Time Frame: 32 weeks of treatment ]Treatment efficacy in reducing adrenal hyperandrogenism
- Fasting Blood Glucose (FG) [ Time Frame: 32 weeks of treatment ]Treatment effect on fasting glucose prior to an oral glucose tolerance test (OGTT)
- 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.
- 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.
- 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
- 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.
- 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.
- Total Cholesterol Levels [ Time Frame: 32 weeks of treatment ]Treatment impact on improving total cholesterol levels
- High Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: 32 weeks of treatment ]Impact of treatment on HDL levels after 32 weeks of treatment
- Triglyceride Levels (TRG) [ Time Frame: 32 weeks of treatment ]Drug effect of TRG levels after 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.
- 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.
- Systolic Blood Pressure [ Time Frame: 32 weeks of treatment ]Treatment impact on systolic blood pressure
- Diastolic Blood Pressure (BP) [ Time Frame: 32 weeks of treatment ]Treatment impact on reducing diastolic blood pressure
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
|United States, Louisiana|
|Baton Rouge, Louisiana, United States, 70817|
|Study Chair:||Peggy Dean, PharmD||Woman's Hospital Foundation IRB|