Clinical Research Directory

Fertility and Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and affects approximately 10% of women worldwide. The diagnosis is based on the Rotterdam criteria established in 2003 and updated in the latest recommendations from the European Society of Human Reproduction (ESHRE) in 2023. The diagnosis of PCOS is based on the presence of 2 of the following 3 criteria: 1. Oligo-anovulation 2. Clinical and/or biological hyperandrogenism 3. Polycystic ovary morphology (PCOM) on imaging It is also the leading cause of anovulatory infertility, with a 15-fold increased risk of infertility. It is therefore a major cause of anovulatory infertility, but its pathophysiological mechanisms remain complex and multifactorial, involving interactions between genetic, metabolic, hormonal, and environmental factors. Prior to embarking on a fertility treatment plan, it is essential to better understand how these various factors influence ovarian function and reproductive capacity in patients with PCOS. Identifying and characterizing factors associated with fertility-such as hormonal profiles, insulin sensitivity, and metabolic markers-could help better predict future fertility and optimize personalized care and fertility outcomes. The aim of this study is therefore to identify modifiable factors influencing the fertility of PCOS patients phenotyped at La Pitié-Salpêtrière hospital.

Polycystic Ovary Syndrome in Type 1 Diabetes

BACKGROUND Functional ovarian hyperandrogenism, including the polycystic ovary syndrome (PCOS), is very prevalent in women with type 1 diabetes (T1D). The pathogenic mechanisms of this association remain unclear. HYPOTHESIS Individual factors expose or protect women with T1D to/from the development of androgen excess and PCOS. Such androgen excess in women with T1D may increase their cardiometabolic risk. MAIN OBJECTIVE Unveiling the pathogenic mechanisms behind functional hyperandrogenism in women with T1D from a sex/gender-medicine and sexual dimorphism perspective. MATERIAL AND METHOS We have designed a cross-sectional comparative clinical study, including 5 groups of study subjects with 12 participans per group: i) Women with T1D \& PCOS. ii) Women with T1D without PCOS. iii) Men with T1D and normal gonadal function. iv) Women with PCOS without diabetes mellitus v) Non-hyperandrogenic control women without T1D. All groups will show similar age and body mass index. T1D groups will be matched for duration of disease. OUTCOMES 1.1 Insulin sensitivity (hyperinsulinaemic euglycaemic clamping). 1.2 Body composition (dual-energy x-ray absorptiometry, bioelectrical impedance analysis \& sonographic studies). 1.3 Ovarian and adrenal steroidogenesis. 2.1 Differential pattern in genetic variants related with insulin signalling and response, inflammation, adiposity, gonadal function, steroidogenesis, and PCOS itself by whole exome sequencing. 2.2 Microbiopsy studies in deep subcutaneous adipose tissue and skeletal muscle tissue: 2.2.1 Differential DNA methylation patterns in genes associated with PCOS. 2.2.2 Differential transcriptomic pattern in genes associated with PCOS. 2.2.3 Differential proteomic patterns in adipose and muscle tissues. 3. Interaction between T1D and PCOS on parameters of metabolic control (intersticial blood glucose monitoring) and morbidities associated with T1D itself.

Comparison of IVF Outcomes Between PPOS and Antagonist Protocols in Women With PCOS

This study aims to compare the outcomes of two ovarian stimulation protocols used in in vitro fertilization (IVF): the progestin-primed ovarian stimulation (PPOS) protocol and the GnRH antagonist protocol.

SCUBE Proteins in Polycystic Ovary Syndrome (IPSOS)

This study investigates circulating levels of SCUBE-1 and SCUBE-3 proteins in women with polycystic ovary syndrome (PCOS) compared with healthy controls. Differences between normoinsulinemic and hyperinsulinemic PCOS subgroups will be evaluated, as well as correlations with clinical and metabolic parameters related to inflammation and cardiovascular risk.

Mobile Application for Women With Polycystic Ovary Syndrome

Objective: The aim is to develop a mobile application based on the Health Promotion Model for the management of PCOS and to determine the effect of this application on improving nutrition and exercise behavior in women with PCOS. Method: The study population will consist of 114 women diagnosed with PCOS according to the Rotterdam criteria (2003) by a specialist in Obstetrics and Gynecology (G power 3.1.9.7). Inclusion criteria are being over 18 years old, female, diagnosed with PCOS, willingness to participate in the study, owning a smartphone with Android or iOS operating system, having digital literacy, and not having a diagnosed psychiatric condition. Exclusion criteria include being pregnant or planning to become pregnant during the study, having musculoskeletal, neurological, respiratory, or cardiovascular diseases, undergoing any surgery or having health issues that could affect physical activity for more than a month, unwillingness to participate in the study for any reason, and not having internet access. Participants will be randomly assigned to either the experimental or control group. The experimental group will receive a PCOS-specific exercise and nutrition program through the mobile app based on the Health Promotion Model, while the control group will receive the program via a pamphlet and it will be applied over 8 weeks. The mobile application will include an exercise program, nutrition counseling, and health coaching for PCOS management, all aligned with the Health Promotion Model. At the beginning and end of the study, participants' blood measurements, anthropometric measurements, physical activity levels, exercise behavior, and adherence to the Mediterranean Diet will be evaluated.

Effects of a Specific Dietary Program on Overweight/Obese Women With Polycystic Ovary Syndrome: A Multicenter, Prospective, Randomized Controlled Clinical Study

The goal of this clinical trial is to investigate the effects of a specific dietary program on overweight or obese patients with polycystic ovary syndrome (PCOS) through a multicenter, randomized, controlled, prospective study design. The main questions it aims to answer are: 1. Does the specific dietary program increase the clinical remission rate of PCOS in overweight or obese patients? 2. Does the specific dietary program improve metabolic and anthropometric outcomes in overweight or obese patients with PCOS compared with conventional intervention? Researchers will compare the effects of a specific dietary program versus conventional intervention on clinical remission rates, metabolic outcomes, and anthropometric measures in overweight or obese patients with PCOS. Participants will: 1. Receive either a specific dietary intervention or conventional intervention for 24 weeks. 2. Undergo assessments every 12 weeks throughout the study period.

Phenotyping of Patients With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the leading endocrine disorder of the reproductive system, affecting 10 to 13% of women of childbearing age. However, there is a significant delay in diagnosis, which may be due to considerable clinical heterogeneity and a lack of information among the general population. The diagnosis is made when two of the three Rotterdam criteria established in 2003 and revised in 2023 are met, namely: 1) menstrual cycle disorders (oligoanovulation) - 2) clinical or biological hyperandrogenism - 3) OPK morphological appearance or elevated anti-Müllerian hormone (AMH) levels, after exclusion of differential diagnoses. PCOS is a condition that carries a risk of metabolic complications and fertility problems due to dysovulation. Patients have an impaired quality of life and are at greater risk of anxiety and depression, which should be screened for systematically.

A Clincial Study Testing Tirzepatide on Reproductive Function and Metabolic Health in Women With PCOS Who Are Overweight or Obese

This clinical study examines whether tirzepatide can improve ovarian dysfunction in premenopausal women with polycystic ovary syndrome (PCOS) who are overweight or have obesity. Tirzepatide is already approved for the treatment of diabetes and obesity, but its effects on ovarian dysfunction in PCOS are not yet known. Participants will be randomly assigned to tirzepatide or placebo in a double-blinded manner. The goal of the study is to demonstrate that tirzepatide, at the maximum tolerated dose, is superior to placebo for improvement of ovarian dysfunction as defined by menstrual irregularity in overweight or obesity-related PCOS. All participants will have a screening visit, followed by 72 weeks of treatment. Treatment includes a 20-week dose-escalation period and a 52-week maintenance period. Lower doses may be used if side effects occur, and the highest tolerated dose will be continued through the maintenance phase. A 4-week safety follow-up will take place after treatment, and long-term follow-up will continue for one year. The study will take place at five clinical trial sites in Germany.

Effect of Magnesium and Levocarnitine on Metabolic and Clinical Outcomes in Women With Polycystic Ovarian Syndrome (PCOS)

Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age and is associated with metabolic abnormalities such as insulin resistance, dyslipidemia, and hormonal imbalance, which may lead to infertility and hirsutism. Despite the availability of several pharmacological treatments, many therapies fail to effectively address the underlying metabolic and endocrine dysfunctions of PCOS. Magnesium and L-carnitine are two essential nutrients that may play a synergistic role in improving insulin sensitivity, glucose metabolism, and lipid profile, as well as reducing oxidative stress and androgen production in women with PCOS. This randomized, triple-blind, placebo-controlled clinical trial aims to evaluate the effects of co-supplementation with magnesium and L-carnitine on glycemic control indices, lipid profile, and hirsutism in women with PCOS. A total of 84 eligible women aged 19-65 years diagnosed with PCOS according to the Rotterdam criteria will be recruited from Shohada Tajrish Hospital, Tehran, Iran. Participants will be randomly assigned to one of three groups: (1) magnesium supplementation (500 mg/day, in two 250 mg doses) plus L-carnitine placebo, (2) L-carnitine supplementation (1000 mg/day) plus magnesium (500 mg/day), or (3) placebo control group. The intervention period will last 12 weeks. Physical activity information will be collected using short form of International Physical Activity Questionnaire (IPAQ) and demographic information through a general information questionnaire. In order to evaluate dietary intake of patients in terms of energy(kcal/(day), carbohydrate(gr/day), protein(gr/day), fat intake(gr/day), saturated fatty acids (SFA) (gr/day), monounsaturated fatty acids (MUFA) (gr/day), polyunsaturated fatty acids (PUFA)(gr/day), Vitamin E (mg/day), Vitamin C (mg/day), Beta-carotene (mg/day) and Vitamin A (mg/day), cupper intake (mg/day), selenium intake (mg/day), and zink intake (mg/day), 24-hr recalls will be completed by interviewing the patient for 3 days (two normal days and a weekend day). Weight will be measured with the minimum dress and without shoes by using a digital balance scale of 100 grams and height will be measured without shoes by meters mounted to the wall with an accuracy of 0.5 centimeters. Then the body mass index will be calculated by dividing the weight (kg) by the square of the height (m), waist circumference will be measured in the narrowest area between the lowest lumbar spine and the iliac bone (cm), systolic and diastolic blood pressure will be measured after 15 minutes of rest, twice using the mercuric barometric measure and the mean will be reported as individual blood pressure. The blood sample will be taken after 12 hours of overnight fasting in three groups for measuring Fasting Blood Sugar (FBS) (mg/dL), lipid profile (mg/dL), Hemoglobin A1c (HbA1C) (percentage), serum insulin concentration (µIU/ml) and insulin resistance. Insulin resistance will be calculated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) formula, and hirsutism score (using the modified Ferriman-Gallwey method) will be assessed at baseline and post-intervention. At the end of the study, counting the remaining capsules, the patient's compliance rate will be evaluated, and patients who have consumed less than 90% of their capsules will be excluded from the analysis.

Effect of Levocarnitine Plus Myoinositol Versus Myoinositol Alone on Hormonal and Insulin Resistance in PCOS Women

The goal of this clinical trial is to learn if combination of levocarnitine and myoinositol works better than myoinositol alone on insulin resistance and hormonal parameters in subfertile women with insulin resistant polycystic ovary syndrome . It will also learn about the safety of drug levocarnitine and myoinositol. The main questions it aims to answer are: Does combined action of levocarnitine and myoinositol improve insulin resistance and hormonal parameters in comparison to myoinositol alone in subfertile women with insulin resistant polycystic ovary syndrome ? What medical problems do participants have when taking drug levocarnitine and myoinositol? Researchers will compare the drug combination of levocarnitine and myoinositol to myoinositol alone to see if combination therapy works better? Participants will: Take drug levocarnitine and myoinositol or a myoinositol alone twice daily for 3 months Visit the clinic once after 3 months for checkups and tests Keep a diary of their symptoms and the number of times.

Efficacy of Oral Contraceptive, Progesterone, and Inositol on Menstrual Regulation in PCOS

This cross-sectional study aims to compare the effectiveness of oral contraceptives, oral progesterone (didrogesterone), and inositol in regulating menstrual cycles among women diagnosed with polycystic ovary syndrome (PCOS). PCOS is a common endocrine disorder affecting reproductive-aged women and is associated with menstrual irregularities, hyperandrogenism, and polycystic ovarian morphology. While oral contraceptives are the mainstay of treatment, their use may be contraindicated in patients with cardiovascular risk factors, liver dysfunction, or in those who desire pregnancy. This study investigates whether oral progesterone and myo-inositol can serve as effective and safer alternatives for menstrual regulation and improvement of ovarian morphology and hyperandrogenic symptoms. A total of 150 women aged 15-40 years with a diagnosis of PCOS will be enrolled and divided into three equal groups: Group 1: Oral contraceptive users Group 2: Oral progesterone users Group 3: Inositol users The study will assess changes in menstrual regularity, ovarian morphology (via ultrasound), and clinical features such as hirsutism and acne before and after treatment.

IVM - Fresh ET (THE SAIGON PROTOCOL) Versus IVF - FET in PCOS Women

Assisted Reproductive Technologies (ART) aim to increase success rates while minimizing patient risks. For women with high AFC or PCOS, conventional IVF carries a high risk of OHSS (Ho et al., 2019). A modern IVF strategy to prevent this uses a GnRH agonist trigger, requiring a "freeze-all" and subsequent FET (Wong et al., 2017). This reduces OHSS risk but can increase time to pregnancy (Vuong et al., 2021) and treatment burden. IVM is a patient-friendly alternative that eliminates OHSS risk by avoiding high-dose gonadotropins. A 2020 trial by Vuong et al. compared CAPA-IVM-FET to conventional IVF-FET in women with high AFC. IVM yielded a comparable live birth rate (35.2%) versus IVF (43.2%), with a 0% OHSS rate in IVM compared to 0.7% in IVF (Vuong et al., 2020). The optimal transfer method (fresh or frozen) in IVM cycles is debated. A 2021 pilot RCT by Vuong et al. found a freeze-only strategy after CAPA-IVM led to a significantly higher live birth rate (60%) than a fresh transfer (20%) (Vuong et al., 2021), but increased time to pregnancy (194 vs. 150 days) (Vuong et al., 2021). A refined CAPA-IVM protocol, which uses no gonadotropins, allowed for fresh embryo transfer in the same cycle, resulting in a numerically higher ongoing pregnancy rate (43.3% vs. 33.3%) than FET (Vuong et al., 2025). This raises an important question: how does a simplified IVM strategy with fresh transfer compare to the established "safety-net" IVF strategy with FET? These two approaches represent opposing clinical philosophies. No large-scale study has yet compared them in women with PCOS. Therefore, this study is designed to compare the SAIGON protocol (gonadotropin-free CAPA-IVM with fresh ET) against a standard GnRH-antagonist IVF protocol with agonist trigger and subsequent FET.

Protein and Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a significant public health problem and is one of the most common hormonal disturbances affecting women of reproductive age. Women with PCOS are often insulin resistant, increasing their risk for cardiometabolic health problems (e.g., type 2 diabetes, heart disease, high blood pressure, sleep apnea, anxiety, depression, and stroke) especially if they are overweight. Lifestyle modifications, including dietary changes and regular physical activity, may alleviate metabolic dysfunction in women with PCOS and are often the first line of management for patients with PCOS. Several studies have identified protein as a key nutrient for regulation of energy balance, maintenance of skeletal muscle mass, and improving cardiometabolic health across the lifespan. However, the effect of increased protein intake (30% of total energy intake) on cardiometabolic health in women with PCOS has not been well-defined and mechanisms for these effects have not been identified. There is an evident need for well-designed, randomized controlled trials evaluating the efficacy of increased protein intake in women with PCOS on markers of cardiometabolic health. Preliminary data from collaborative projects with the investigators on this proposal suggest that increasing protein in the diet has the potential to improve markers of cardiometabolic health, potentially through improvements in body composition and/or changes in cortisol, energy metabolism, inflammation, and neurological regulators

Appetite Response to Meals With Different Protein Sources in Women With PCOS

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance, hyperandrogenism, and reproductive dysfunction. Dietary strategies that improve postprandial insulin and glucose responses are central to managing metabolic symptoms in PCOS. Meals higher in protein can attenuate postprandial glycemia and enhance satiety, but the effects may vary by protein source. Animal sources of protein typically have higher essential amino acid content and insulinogenic potential, whereas plant proteins offer fiber and phytochemicals that may influence glycemic dynamics differently. Few studies have directly compared the acute metabolic effects of plant versus animal protein in women with PCOS. Given the distinct pathophysiology of PCOS, extrapolating findings from healthy populations may be misleading. Understanding protein-specific effects on postprandial insulin, glucose, and appetite-regulating hormones in this group is essential for targeted nutrition guidance. Additionally, plant-based diets are increasingly promoted for cardiometabolic health, but their acute effects in insulin-resistant women remain underexplored. This study will assess whether plant and animal protein meals elicit differential postprandial responses in women with PCOS. Findings may inform dietary recommendations aimed at improving metabolic outcomes in this high-risk population.

Strengthening Healthy Emotional Co-regulation of Mothers With PCOS and Obesity and Their Infants

It is both timely and important to invest in interventions that can improve healthy emotional co-regulation. It is proposed to evaluate the feasibility and limited efficacy of an adapted, brief, multimodal intervention: ECoFam (Emotional connection and Co-regulation for Families). Evidence from the US suggests intervention effects on maternal and infant outcomes that are large in effect size (i.e., Cohen's d \>0.6 for increasing emotional connection and decreasing maternal depressive symptoms) (21-23). The study results will directly translate evidence into practice and, if found feasible, allow rapid scaling-up. Objectives: 1. Build capacity for implementation of a novel diagnostic screening tool for emotional co-regulation, the uWECS, as part of clinical follow-up for mother-infant dyads with high fibrobesity risk in Finland. 2. Test the feasibility and limited efficacy of the brief, multimodal ECoFam intervention to foster healthy emotional co-regulation between mothers with PCOS and obesity and their infants.

Optimizing Metformin Use in Polycystic Ovary Syndrome

The goal of this clinical trial is to learn if a metformin dose of 1500 mg or 2250 mg per day is better to treat polycystic ovary syndrome (PCOS) in adults. It will also learn about the adverse effects of metformin. The trial aims to evaluate which metformin dose is better for: 1. improving biochemical and clinical outcomes 2. gastrointestinal side-effects 3. mental health and quality of life Participants will: * Be randomized to take metformin at a dose of either 1500mg or 2250mg every day for 6 months * Visit the clinic three times during the trial for checkups and tests * Answer questionnaires on menstrual cyclicity, mental health, quality of life and side-effects

Mechanism of Red Yeast Rice Regulating Intestinal Indole Metabolism Pathway to Improve Chronic Inflammation in Polycystic Ovary Syndrome

The aim of this study is to elucidate the effects of red yeast rice on the improvement of symptoms in patients with polycystic ovary syndrome（PCOS）, and to analyze the dose-response relationship between intestinal microbiota and its metabolite, hydroxyindole, and clinical indicators of PCOS. The main questions it aims to answer are: How effective is red yeast rice in treating PCOS? Does the indole metabolic pathway of gut microbiota play a crucial role in the improvement of PCOS symptoms by red yeast rice? Participants will take 6 grams of red yeast rice daily for 6 months, and records will be kept of their PCOS clinical symptoms and indicators before the intervention, at the 3rd month post-intervention, and at the 6th month post-intervention. Additionally, biological samples from feces and serum will be collected at these time points.

Evaluation of MG53 (TRIM72) Levels in Women With Polycystic Ovary Syndrome: An Observational Study

Purpose of the Study: This study is being conducted to examine a protein called MG53 (also known as TRIM72) in women with polycystic ovary syndrome (PCOS). MG53 is involved in cell membrane repair and may play a role in insulin resistance, which is common in PCOS. Study Procedures: Women between 18 and 45 years of age will be invited to participate. The study population will include both women diagnosed with PCOS and healthy controls. A single blood sample (approximately 5 mL) will be collected from each participant. MG53 levels will be measured using an ELISA laboratory assay. Significance of the Study: Analysis of MG53 levels in relation to hormonal and metabolic markers may help determine whether MG53 is associated with insulin resistance and other characteristics of PCOS.

Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder affecting women of reproductive age, with a prevalence of 10 to 13%. PCOS is characterized by irregular menstrual cylcles/ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. For infertile patients seeking ovulation induction, letrozole is the drug of first choice. For PCOS patients not seeking pregnancy, there exists a variety of treatments to alleviate symptoms. It has been demonstrated that artemisinin derivatives can promote energy expenditures and insulin sensitivity by activating thermogenic adipocytes, thereby protecting against diet-induced obesity and metabolic disorders in rodents. Recently, we showed in a single arm pilot study including 19 PCOS-patients, that dihydroartemisinin ameliorated hyperandrogenemia reduced antral follicle count and normalized menstrual cycles. Based on these findings, we aim to evaluate the efficacy of dihydroartemisinin in women with PCOS in a placebo controlled randomized clinical trial. The primary outcome is return of regular menstrual cycles within 6 months after start of treatment, with antral follicle count and metabolic profile being secondary outcomes. The results will potentially impact the standard of care for patients diagnosed with PCOS.

Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for PCOS

This trial will study the safety and efficacy of cultured allogeneic adult umbilical cord derived mesenchymal stem cells delivered intravenously for the treatment of Polycystic Ovary Syndrome.

App Impact on Quality of Life and Symptoms in PCOS

This study investigates the influence of a PCOS app on the quality of life and symptoms of individuals with polycystic ovary syndrome (PCOS). The intervention group can use the app over the study period of twelve weeks in addition to care-as-usual (CAU). In the control group, this is compared with no use of the PCOS-App for a twelve-week period, that is, care-as-usual only/ continuation of the current treatment (waitlist design). The aim is to evaluate the effectiveness of the app and to gain insights for the design of future studies. The study is expected to last seven months and include 220 participants.

A Clinical Trial to Evaluate the Efficacy, Tolerability, and Safety of a Fixed Dose Combination of Spironolactone, Pioglitazone & Metformin (SPIOMET) in Polycystic Ovary Syndrome (PCOS)

This is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase II clinical trial to evaluate the efficacy, tolerability, and safety of a fixed dose combination of Spironolactone, Pioglitazone and Metformin (SPIOMET) for adolescent girls and young adult women with polycystic ovary syndrome. Study description: Currently, there is no European Medicines Agency /U.S. Food and Drug Administration (FDA)-approved therapy for polycystic ovary syndrome in adolescent girls and young adult women. Oral contraceptives (OCs) are prescribed off-label to approximately 98% of AYAs with PCOS, including those without pregnancy risk. OCs alleviate key symptoms by inducing a pharmacological combination of anovulatory subfertility, regular pseudo-menses, and extreme elevations of sex hormone-binding globulin (SHBG), but OCs do not revert the underlying pathophysiology, and patients remain at risk for post-treatment subfertility and possibly, for lifelong co-morbidities. Given the key role of hepato-visceral fat excess in the pathogenesis of PCOS, the prime aim of the treatment should be to achieve a preferential loss of central fat, which should in turn normalise the entire PCOS phenotype. Recent evidence disclosed that a treatment consisting of a fixed low-dose combination of two insulin sensitisers \[pioglitazone (PIO) and metformin (MET), with different modes of action\], and one mixed anti-androgen and anti-mineralocorticoid (spironolactone), was superior to an OC in normalising the PCOS phenotype, including ovulation rates and hepato-visceral fat. The study's main goals are to assess the efficacy, tolerability and safety of a new treatment (SPIOMET) for adolescent girls and young adult women with polycistic ovarian syndrome; the comparison (in this order) of each SPIOMET, spironolactone and pioglitazone (SPIO) and PIO over placebo; and in addition, the comparison of SPIOMET over PIO and over SPIO (in this order). Primary Objective: To test the efficacy of SPIOMET in normalising ovulation rate in adolescents and young adult women with PCOS. Secondary Objectives: To test the efficacy of SPIOMET in normalising the endocrine-metabolic status, to describe the drug safety profile and to assess the adherence and subjective acceptability, as well as the quality of life of the participating subjects.