Effect of levothyroxine and hypocaloric diet for the treatment of obesity.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

4 Sep 2025 → ongoing

Decision date (initial)

2024-09-20

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the effect of adjuvant treatment with levothyroxine together with a hypocaloric diet and physical exercise recomendations, compared with placebo together with the same lifestyle strategy, on weight loss and body composition at 3 months, 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.

Secondary objectives 10

1. To evaluate whether levothyroxine treatment prevents weight regain compared to placebo in patients who previously underwent a weight loss intervention.
2. To evaluate the changes in the stage of obesity (obesity type I and II), after the intervention for weight loss (levothyroxine versus placebo).
3. To analyze the differences in lipid and carbohydrate metabolism, markers of inflammation and adipokines, and blood pressure patterns among obese subjects treated with levothyroxine versus placebo.
4. To assess changes in resting energy expenditure after treatment with levothyroxine compared with placebo.
5. To assess the safety of levothyroxine as a treatment for obesity.
6. To assess 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 to analyze mitochondrial DNA in adipose tissue.
7. To identify biomarkers able to differentiate hypo and hyperresponders to levothyroxine treatment.
8. To identify whether gender is a determining factor in the response to the intervention to the above objectives: 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.
9. Recognize whether gender marks a trend between hypo- and hyperresponders to levothyroxine treatment.
10. To determine changes in quality of life (EuroQol-5D quality of life questionnaire).

Conditions and MedDRA coding

Metabolic disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Subjects between 25-60 years old.
2. Grade I-II obesity (defined by a BMI between 30-39.9 Kg/m2).
3. Subclinical hypothyroidism (TSH between 5 and 10 with normal peripheral hormones) or euthyroid with TSH in the highest tertile of the population reference levels.
4. Provide informed consent before inclusion in this study.

Exclusion criteria 17

1. 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).
2. Previous diagnosis of thyroid disease (hyperthyroidism, clinical hypothyroidism or previously treated with levothyroxine).
3. Be receiving treatment with levothyroxine or any hypoglycaemic or have received either of the two up to 3 months before entering the study.
4. Regular consumption of probiotics or prebiotics or the consumption of antibiotics during the 3 months prior to inclusion.
5. Previous history of cancer (except basalioma) in the last 5 years or active cancer of any kind.
6. 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.
7. Establish cardiovascular disease, such as cerebrovascular accidents, ischemic heart disease, peripheral artery disease, among others.
8. Previous history of atrial fibrillation or any arrhythmia.
9. 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.
10. Any degree of heart failure; baseline resting heart rate greater than 85 bpm; renal insufficiency with glomerular filtration less than 60 ml/min.
11. Known HIV, HBV, HCV infection.
12. Evidence of acute inflammatory disease. Presence of inflammatory bowel disease.
13. Serious underlying diseases, which at the researcher´s discretion, could affect the patient´s ability to participate in the study.
14. Evidence of drug or alcohol abuse; expectation of reduced life (<12 months). Impossibility of following recommended diet; inability to follow program visits.
15. Positive screening pregnancy test, pregnant or expectation of pregnancy and lactating women.
16. Inability or unwillingness to give informed consent.
17. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Weight loss (measured in percentage (%) and kilograms (kg)) and body composition changes (BMI, waist/hip circumference, fat mass, fat free mass, body water by impedance measurement) from baseline to the end of intervention program at 3 months (sample size: 286 subjects).

Secondary endpoints 11

1. Weight Regain Prevention Rate in patients who previously underwent a weight loss intervention (the same parameters as on the endpoint will be measured) from month three untill the end of the treatment.
2. Changes in the stage of obesity (obesity type I and II) measured by changes in BMI.
3. Changes in cardiovascular risk factors: lipids, blood pressure, glucose, HbA1c, HOMA-IR, adipokines and inflammation markers.
4. Changes in resting energy expenditure determined by indirect calorimetry.
5. Differences in the degree of physical activity quantified by accelerometry.
6. Changes in cardiac function: heart rate, ventricular extrasystoles, QT interval (EKG); and the apparition of side effects and adverse reactions.
7. Changes in metabolic activity of adipose tissue.
8. Gut microbiota analysis, epigenetic studies and analysis of genes related to obesity.
9. Changes in nitrogen balance.
10. Define gender, as a determining factor in reaching the primary endpoint and secondary outcomes.
11. Changes in quality of life (EuroQol-5D quality of life questionnaire).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Sponsor organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Address

Calle De Severo Ochoa 35, Parque Tecnologico De Andalucia Parque Tecnologico De Andalucia

City

Malaga

Postcode

29590

Country

Spain

Scientific contact point

Organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Contact name

Isabel María Cornejo

Public contact point

Organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Contact name

Isabel María Cornejo

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications