Evaluation of Levothyroxine Sodium as an Adjunct to Hypocaloric Diet in Obesity Management in Patients with Subclinical Hypothyroidism or Euthyroidism
- Trial ID
- 2024-514377-22-00
- Protocol
- LEVOBESITY
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **levothyroxine** as an adjuvant treatment, in conjunction with a hypocaloric diet and physical exercise recommendations, compared to placebo with the same lifestyle strategy, on weight loss and body composition over a 3-month period in subjects with obesity and subclinical hypothyroidism or euthyroidism with TSH levels in the upper tertile of the normal range for the population without thyroid disease. This is clinically relevant as it aims to determine the potential benefits of levothyroxine in enhancing weight management strategies in individuals with specific thyroid function profiles.
Secondary objectives include:
- Evaluating whether levothyroxine treatment prevents weight regain compared to placebo in patients who previously underwent a weight loss intervention.
- Assessing changes in the stage of obesity (obesity type I and II) after the intervention for weight loss.
- Analyzing differences in lipid and carbohydrate metabolism, markers of inflammation and adipokines, and blood pressure patterns among obese subjects treated with levothyroxine versus placebo.
- Assessing changes in resting energy expenditure after treatment with levothyroxine compared with placebo.
- Evaluating the safety of levothyroxine as a treatment for obesity.
- Assessing gene expression and protein abundance changes in adipose tissue samples related to their lipogenic and lipolytic capacity, adipokines, thyroid receptor and browning biomarkers of adipose tissue, and analyzing mitochondrial DNA in adipose tissue.
- Identifying biomarkers able to differentiate hypo and hyperresponders to levothyroxine treatment.
- Determining whether gender is a determining factor in the response to the intervention regarding weight loss, changes in body composition, prevention of weight regain, changes in the stage of obesity, as well as changes in lipid and carbohydrate metabolism or markers of inflammation and hormonal profile.
- Recognizing whether gender marks a trend between hypo- and hyperresponders to levothyroxine treatment.
- Determining changes in quality of life using the EuroQol-5D quality of life questionnaire.
Participants
The clinical trial involves a study population comprising **subjects** aged between 25 and 60 years, including both male and female participants. The trial focuses on individuals with **Grade I-II obesity**, defined by a BMI ranging from 30 to 39.9 kg/m², and those diagnosed with **subclinical hypothyroidism** or euthyroid individuals with TSH levels in the upper tertile of the normal range for the population without thyroid disease. Participants are required to adhere to a hypocaloric diet and engage in physical exercise as part of the lifestyle strategy. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed to evaluate the effect of **levothyroxine sodium** as an adjuvant therapy to a hypocaloric diet in the treatment of obesity. This study is a randomized, placebo-controlled trial with a double-blind design, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to last for a total duration of 9 months, with the primary intervention phase lasting 3 months. The study aims to assess weight loss and body composition changes in subjects with obesity and subclinical hypothyroidism or euthyroidism with TSH levels in the upper tertile of the normal range.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age (25-60 years), obesity grade (BMI between 30-39.9 kg/m²), and thyroid function. Following successful screening, participants will be randomized to receive either levothyroxine sodium or a placebo, both administered orally in tablet form. The primary endpoint will be evaluated at the end of the 3-month intervention period, with follow-up visits scheduled to monitor secondary endpoints, including weight regain prevention, changes in cardiovascular risk factors, and metabolic activity. The end-of-study visit will occur at the conclusion of the 9-month period to assess long-term outcomes and any adverse effects.
Participant involvement is expected to last the full 9 months unless early termination is warranted. Conditions for early termination include significant adverse reactions, non-compliance with the study protocol, or withdrawal of consent. The study will adhere to ethical guidelines, ensuring informed consent is obtained from all participants prior to inclusion. The trial's primary and secondary endpoints will be measured using standardized methods, including body composition analysis, cardiovascular assessments, and metabolic evaluations, to ensure the reliability and validity of the results.
Treatment
The clinical trial involves the administration of **levothyroxine sodium** as the experimental medication. The product, marketed under the name "Eutirox 88 microgramos comprimidos," is formulated as a **tablet**. Each tablet contains 88 micrograms of levothyroxine sodium, a chemical substance, and is administered orally. The maximum daily dose is 88 micrograms, with a total treatment period of up to 9 months. The primary objective of the trial is to evaluate the effect of levothyroxine as an adjuvant therapy to a hypocaloric diet and physical exercise recommendations in subjects with obesity and subclinical hypothyroidism or euthyroidism with TSH levels in the upper tertile of the normal range.
In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is composed of **microcrystalline cellulose**, also in tablet form, and is administered orally. The placebo tablets are designed to match the appearance and administration schedule of the levothyroxine tablets to ensure blinding. The maximum daily dose of microcrystalline cellulose is 500 milligrams, with a total treatment period of up to 9 months. The placebo serves as a control to assess the efficacy of levothyroxine in conjunction with lifestyle modifications on weight loss and body composition.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on evaluating weight loss and body composition changes in subjects with obesity and subclinical hypothyroidism or euthyroidism. These changes will be measured in terms of percentage and kilograms of weight loss, as well as alterations in body mass index (BMI), waist/hip circumference, fat mass, fat-free mass, and body water, using impedance measurement. These assessments will be conducted from baseline to the end of the intervention program at 3 months, with a sample size of 286 subjects.
Secondary endpoints will include the Weight Regain Prevention Rate, assessed from month three until the end of the treatment, using the same parameters as the primary endpoint. Additional secondary endpoints will evaluate changes in obesity stage, cardiovascular risk factors (including lipids, blood pressure, glucose, HbA1c, HOMA-IR, adipokines, and inflammation markers), and resting energy expenditure determined by indirect calorimetry. The trial will also assess differences in physical activity levels using accelerometry, changes in cardiac function (heart rate, ventricular extrasystoles, QT interval via EKG), and the occurrence of side effects and adverse reactions. Further assessments will include changes in metabolic activity of adipose tissue, gut microbiota analysis, epigenetic studies, analysis of genes related to obesity, changes in nitrogen balance, and the impact of gender on reaching the primary and secondary outcomes. Quality of life changes will be measured using the EuroQol-5D quality of life questionnaire.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects between 25-60 years old.
- Grade I-II obesity (defined by a BMI between 30-39.9 Kg/m2).
- Subclinical hypothyroidism (TSH between 5 and 10 with normal peripheral hormones) or euthyroid with TSH in the highest tertile of the population reference levels.
- Provide informed consent before inclusion in this study.
Exclusion Criteria
- Previous diagnosis of diabetes mellitus (defined by HbA1c ≥6.5% or baseline blood glucose ≥=126mg/dl or blood glucose after 2 hours of oral glucose tolerance test ≥200 mg/dl).
- Previous diagnosis of thyroid disease (hyperthyroidism, clinical hypothyroidism or previously treated with levothyroxine).
- Be receiving treatment with levothyroxine or any hypoglycaemic or have received either of the two up to 3 months before entering the study.
- Regular consumption of probiotics or prebiotics or the consumption of antibiotics during the 3 months prior to inclusion.
- Previous history of cancer (except basalioma) in the last 5 years or active cancer of any kind.
- Chronic liver disease with impaired liver function detected: total bilirubin levels ≥2.0 mg/dl or AST levels three times higher than the normal upper limit.
- Establish cardiovascular disease, such as cerebrovascular accidents, ischemic heart disease, peripheral artery disease, among others.
- Previous history of atrial fibrillation or any arrhythmia.
- Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) despite adequate antihypertensive therapy. For the evaluation of this criteria will be considered the ABPM measures during the screening period.
- Any degree of heart failure; baseline resting heart rate greater than 85 bpm; renal insufficiency with glomerular filtration less than 60 ml/min.
- Known HIV, HBV, HCV infection.
- Evidence of acute inflammatory disease. Presence of inflammatory bowel disease.
- Serious underlying diseases, which at the researcher´s discretion, could affect the patient´s ability to participate in the study.
- Evidence of drug or alcohol abuse; expectation of reduced life (<12 months). Impossibility of following recommended diet; inability to follow program visits.
- Positive screening pregnancy test, pregnant or expectation of pregnancy and lactating women.
- Inability or unwillingness to give informed consent.
- Patients can leave the study at any time by voluntary withdrawal. The main reason for withdrawn must be recorded on the appropriate page of the data collection document. The reasons for the patient's withdrawn by the investigator include, but are not limited to, the following: - Presence of hyperthyroidism symptoms and signs of overt hyperthyroidism (it will be confirmed by analysis). - Non-compliance by the patient and/or researcher with the study procedures and guidelines. - Any significant adverse event that compromises the patient's safety or their ability to participate in the study. - The investigator's determination that continuing is not in the interest of the patient. In addition to the aforementioned, the Investigator (IP) may withdraw any patient from the study if, in their medical judgment, remaining in the trial may be detrimental to the patient's health.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 01 Jan 2025 | 286 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Eutirox 88 microgramos comprimidos | Test | COMPRIMIDOS | ORAL | 88 | 9 | PRD10032844 |
MICROCRYSTALLINE CELLULOSE | Placebo | — | ORAL | 500 | 9 | SUB12626MIG |