Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules in Type 2 Diabetes

NCT ID: NCT04298684

Last Updated: 2020-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-01

Study Completion Date

2024-07-01

Brief Summary

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A 2-years prospective, randomized and multicentric study will be performed to assess the efficacy of metformin compared to sitagliptin on benign thyroid nodules size ≥ 2 cm, in newly diagnosed patients with type 2 diabetes.

Detailed Description

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Previous studies reported that prevalence of thyroid nodules (TN) is increased in patients with insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, there are no guidelines for the management of TN in this target population. In 2013, the French National Health Insurance reported that thyroid surgery procedures for benign nodules have increased unjustifiably. The impact of such surgery on the patients could be serious, with psychological repercussions and risks of surgical complications and the need of a substitutive lifetime hormonal treatment. The investigators hypothesize that metformin may reduce the need of TN surgery by decreasing benign TN size through a reduction of IR profile. A 2-years multicentric prospective study will be conducted to compare efficacy of metformin versus sitagliptin on benign thyroid nodules size in patients with initial benign thyroid nodules ≥ 2 cm. The percentage of thyroid surgery avoided, IR profile measured by Homeostasis Model Assessment of Insulin Resistance-Index (HOMA-IR-index) and adipokines concentrations will be also collected at inclusion ad at 2 years. The Primary outcome will be the percentage of patients in each group who had at least a 20% decrease in one or more nodules of more than 2 cm at 2 years. Several secondary outcomes will be registered: percentage of thyroid surgery observed in each group at 2 years, number of new TN (≥ 10mm) after 2 years of follow-up , percentage of metabolic syndrome before and after treatment, proportion of subjects with improvement of the HOMA-IR index and adipokine concentrations, plasmatic thyroid-stimulating hormone (TSH), T4 and T3 levels evolution, percentage of insulin like growth factor-1 (IGF-1) and adiponectin receptor expression in thyroid tissues after TN surgery.

Conditions

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Diabetes Mellitus, Type 2 Thyroid Nodule (Benign)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicenter, prospective open-label study evaluating the efficacy of metformin compared to sitagliptin on benign TN growth in subjects with T2DM. After written approval, subjects with T2DM who meet the eligibility criteria will have a thyroid ultrasound. Subjects with TN of at least 2 cm and 2 benign cytology results after fine-needle aspiration, will be included after a run-in period of 1 month with a daily basal insulin therapy in order to reduce glucotoxicity. If the Hb1Ac levels remain above 8%, the subjects will not be included. After inclusion, a central randomization will allow subjects to benefit from either metformin (group 1) or sitagliptin (group 2). In both cases, the standard nutritional care and physical activity recommendations (150 minutes of physical activity per week) will be recalled. If HbA1c levels \> 8% during the follow-up, treatment by gliclazide will be introduce (LP30mg). A follow-up schedule will be given to the included patient for future visits.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Metformin

In arm 1, the subjects will receive metformin at the initial dose of 500mg x 2 / day, which will be increased weekly to 500mgx3 / day and then 1gx2 / day in order to obtain the minimum effective dose on glycemic control.

Group Type EXPERIMENTAL

METFORMIN

Intervention Type DRUG

After inclusion, a central randomization will allow subjects to benefit from either metformin (group 1) or sitagliptin (group 2). A follow-up schedule will be given to the included patient for future visits. thyroid ultrasonography to analyze the TN evolution in the 2 groups.

In arm 1, the subjects will receive metformin at the initial dose of 500mg x 2 / day, which will be increased weekly to 500mgx3 / day and then 1gx2 / day in order to obtain the minimum effective dose on glycemic control. In case of intolerance, the tolerated and effective dose will be taken back provided an effective glycemic control.

A classic follow-up will be done every 3 months. Thyroid US and measure of HOMA-IR index will be done every 6 months for 2 years. If the goal of HbA1c will not achieved, a treatment with glicazide will be introduced.

Sitagliptin

In arm 2, sitagliptin will be prescribed at 100mg / day. A classic follow-up will be done every 3 months.

Group Type PLACEBO_COMPARATOR

Sitagliptin

Intervention Type DRUG

After inclusion, a central randomization will allow subjects to benefit from either metformin (group 1) or sitagliptin (group 2). A follow-up schedule will be given to the included patient for future visits. thyroid ultrasonography to analyze the TN evolution in the 2 groups.

In arm 2, sitagliptin will be prescribed at 100mg / day. A classic follow-up will be done every 3 months. Thyroid US and measure of HOMA-IR index will be done every 6 months for 2 years. If the goal of HbA1c will not achieved, a treatment with glicazide will be introduced.

Interventions

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METFORMIN

After inclusion, a central randomization will allow subjects to benefit from either metformin (group 1) or sitagliptin (group 2). A follow-up schedule will be given to the included patient for future visits. thyroid ultrasonography to analyze the TN evolution in the 2 groups.

In arm 1, the subjects will receive metformin at the initial dose of 500mg x 2 / day, which will be increased weekly to 500mgx3 / day and then 1gx2 / day in order to obtain the minimum effective dose on glycemic control. In case of intolerance, the tolerated and effective dose will be taken back provided an effective glycemic control.

A classic follow-up will be done every 3 months. Thyroid US and measure of HOMA-IR index will be done every 6 months for 2 years. If the goal of HbA1c will not achieved, a treatment with glicazide will be introduced.

Intervention Type DRUG

Sitagliptin

After inclusion, a central randomization will allow subjects to benefit from either metformin (group 1) or sitagliptin (group 2). A follow-up schedule will be given to the included patient for future visits. thyroid ultrasonography to analyze the TN evolution in the 2 groups.

In arm 2, sitagliptin will be prescribed at 100mg / day. A classic follow-up will be done every 3 months. Thyroid US and measure of HOMA-IR index will be done every 6 months for 2 years. If the goal of HbA1c will not achieved, a treatment with glicazide will be introduced.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients with T2DM aged 18 to 65 years;
* Uncomplicated T2DM, evolving for less than 3 years;
* Patients with HbA1c levels between 7 and 8% (after the run-in period)
* Patients with at least one TN ≥ 2 cm non-cystic, whose benignity will be confirmed by a fine-needle aspiration cytology performed twice regardless of ultrasound TIRADS score;
* Naive subjects of any treatment: never received an anti-diabetic treatment OR received an anti-diabetic treatment of less than 30 days since diagnosis OR did not receive an anti-diabetic treatment during the 30 days before screening;
* Patients with a creatinine clearance \> 60 ml/min;
* Informed and written consent signed by the patient and the investigator;
* Affiliation to the national social health system or equivalent.

Exclusion Criteria

* Subjects without adequate or impaired decisional abilities for consent to research and placed under guardianship, trusteeship or safeguard of justice
* Pregnant or breastfeeding woman
* Woman of childbearing potential without effective contraception (estroprogestative, presentative, intrauterine device)
* Suspect thyroid nodules in ultrasound (TIRADS 4 to 5) with confirmation after a fine-needle aspiration cytology;
* Thyroid function abnormalities or a history of thyroid disease;
* Thyroid nodules whose size or symptoms (compressive signs) require surgery
* Ioduria \<100ug /L
* Thyroid autoimmunity: positive anti-peroxidase, thyroglobulin or anti-TSH receptors antibodies
* Levothyroxine treatment
* History of cervical radiotherapy or thyroid surgery
* Type 1 diabetes
* Insulin deficiency
* History of hypersensitivity to one of the active substances
* History of pancreatitis
* Obesity linked to endocrine disease
* Presence of severe complications of T2DM (ischemic heart disease, heart failure with reduced left ventricular ejection fraction, severe lower extremity arteritis, gangrene, retinopathy, end-stage renal failure, cerebrovascular accident)
* HbA1c levels \> 8% after the run-in period
* Liver diseases (liver failure, cirrhosis, viral hepatitis B or C)
* Acute alcoholic intoxication, chronic alcoholism
* Psychiatric diseases (depression, schizophrenia)
* Neurological diseases (epilepsy, demyelinating diseases, etc.)
* Treatment influencing the morphology or thyroid function: corticosteroids, lithium, iodized products etc. ...
* Acute conditions that may impair renal function such as: dehydration, severe infection, shock
* Respiratory failure
* Metabolic acidosis
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Hospitalier Universitaire de la Guadeloupe

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fritz-Line FLV VELAYOUDOM, MD

Role: STUDY_DIRECTOR

CHU de la Guadeloupe

Locations

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CHU Bordeaux

Bordeaux, , France

Site Status

CHU Limoges

Limoges, , France

Site Status

University Hospital Center of Guadeloupe

Pointe-à-Pitre, , Guadeloupe

Site Status

CHU de la Réunion

Saint-Pierre, , Reunion

Site Status

Countries

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France Guadeloupe Reunion

Central Contacts

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Valerie VS HAMONY SOTER

Role: CONTACT

+590590934686

Mélanie MP PETAPERMAL

Role: CONTACT

Facility Contacts

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Bogdan BC CATARGI, MD PhD

Role: primary

Marie-Pierre MT TEISSIER, M.D. Ph D

Role: primary

+335 55 05 68 51

Valérie VS SOTER, Project Manager

Role: primary

0590 93 46 86

Melanie MP PETAPERMAL, Monito manager

Role: backup

0590 93 46 86

Xavier XD DEBUSSCHE, MD PHD

Role: primary

References

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Other Identifiers

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2019-000676-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PAP_RI1_2019/1

Identifier Type: -

Identifier Source: org_study_id

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