Evaluation of Metformin Effect on the Fertility of Women Treated With 131I for Thyroid Cancer

NCT ID: NCT05468554

Last Updated: 2022-10-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2026-04-30

Brief Summary

This study is aimed to investigate the metformin effect on the fertility of women treated with 131 I for thyroid cancer

Detailed Description

One of the most common types of endocrine cancer, especially in young women, is thyroid cancer. More than 90% of all thyroid cancers are differentiated thyroid cancers (DTC), including papillary thyroid cancer (PTC) and follicular cancer. Papillary thyroid cancer is considered as indolent tumour as progression free survival is 10 years of 98%. As per current knowledge and basing on current literature most of the PTC are considered to be low incidence of recurrence or metastasis, however, there are more invasive/aggressive types with very specific pathological and molecular characteristics. The aggressive variants of PTC were strictly associated with higher rates of extrathyroid extension, multifocality, and nodal and distant metastasis. Thyroidectomy followed by radioactive iodine 131 (131I) therapy, in higher stages of PTC disease to ablate residual thyroid cancer or treat metastases, significantly increase survival Metformin (1,1-dimethylbiguanide) is an oral antihyperglycemic drug. Orally administered metformin is absorbed into the blood in 40-60% of the drug dose. Maximum blood levels are reached after approximately 2.5 hours for the immediate-release formulation and 7 hours for the prolonged-release tablets. It is not metabolised in the liver, however, it is excreted unchanged by the kidneys, mainly through the renal tubules. Metformin is used in patients with type 2 diabetes and prediabetes as well as in insulin resistant state and in women with polycystic ovary syndrome (PCOS). Metformin works by lowering level of glucose in the blood by lowering its production by the liver and increasing the sensitivity to insulin by muscle and fat tissue. It also has a beneficial effect on serum lipids by reducing the concentration of triglycerides, total cholesterol, LDL-cholesterol and VLDL. Additionally, this drug has also several other biological effects such as anti-inflammatory, anticancer, hepatoprotective, cardioprotective, otoprotective, radioprotective and radio-sensitising.

Currently there is also a large evidential material for effectiveness of metformin therapy in re-establishing of reproductive functions and fertility in women with polycystic ovary syndrome.

Having proved the metformin restore of ovulation in PCOS and has antioxidant properties there are indications that metformin can be a therapy which will helps to maintain ovary follicle number on acceptable level. At present, there are no performed studies concerned on the evaluation of the potential beneficial effect of metformin application impact on fertility parameters in the group of women treated with 131I. Therefore, the proposed study will assess the effect of metformin intervention on the indirect parameters of fertility of women treated with 131I for papillary thyroid cancer

Conditions

Thyroid Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Metformin

patients qualified to receive metformin and 131I treatment

Group Type: EXPERIMENTAL

metformin

Intervention Type: DRUG

Metformin will be used 3 times a day (3x500mg), starting in the first week with 1x1 tablet (1x500 mg for breakfast), in the second week, 2x1 tablet (500 mg for breakfast and 500 mg for dinner), from the 3rd week 3x1 tablet. (3x500mg with main meals). A gradual escalation of the dose is planned to the point of developing drug intolerance or toxicity that is unacceptable to the patient.

Radioactive iodine (I-131)

Intervention Type: RADIATION

Patients qualified to receive 131I treatment

Placebo

patients receiving placebo and 131 I treatment

Group Type: ACTIVE_COMPARATOR

Radioactive iodine (I-131)

Intervention Type: RADIATION

Patients qualified to receive 131I treatment

Observational

observation group, patients after thyroidectomy, characterized by low risk of cancer progression, in this case, not qualified for 131I treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

metformin

Metformin will be used 3 times a day (3x500mg), starting in the first week with 1x1 tablet (1x500 mg for breakfast), in the second week, 2x1 tablet (500 mg for breakfast and 500 mg for dinner), from the 3rd week 3x1 tablet. (3x500mg with main meals). A gradual escalation of the dose is planned to the point of developing drug intolerance or toxicity that is unacceptable to the patient.

Intervention Type: DRUG

Radioactive iodine (I-131)

Patients qualified to receive 131I treatment

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Female subjects in reproductive age >18 <45.
• Subjects with diagnosed papillary thyroid carcinoma with various pathological, stage TNM (I-II).
• Subjects not treated with 131I.
• Serum TSH concentration 0.1-4.9 mU/l.
• Willingness to comply with protocol procedures.

Exclusion Criteria

• Hypersensitivity to metformin.
• Subjects with polycystic ovarian syndrome or other diseases of the ovaries (primary / secondary ovarian failure).
• Subjects taking metformin during last week.
• Subjects with liver malfunction and abnormal hepatitis marker results (ALT and AST activity >3ULN.
• Subjects with eGFR below 45ml/min/1.73m2.
• Subjects with lactic acidosis or having history of metabolic acidosis.
• Subjects with serum AMH concentration below lower range norm.
• Subjects with history of congestive heart disease NYHA stage III/IV.
• Subjects with acute myocardial ischemia (CCS 3-4).
• Subjects with history of sepsis or severe infection.
• Subject with lung disease (uncontrolled asthma based on GINA 2000 Guidelines and COPD GOLD ≥ 3 stage).
• Positive result of pregnancy test or pregnancy planned during the study.
• Alcohol or other substance dependent syndromes.
• BMI <18.5 kg/m2.
• Accompanying diseases with poor prognosis in the opinion of the researcher.
• As per Investigator (or his designee) judgement, subject cannot participate in the study due to reasons (i.e. medical, psychiatric and/or social reason).
• Unreliability or lack of cooperation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Agency, Poland

OTHER_GOV

Sponsor Role: collaborator

Medical University of Bialystok

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Agnieszka Adamska, Assoc.Prof.

Role: PRINCIPAL_INVESTIGATOR

Medical University of Bialystok

Locations

Department of Endocrinology, Diabetology and Internal Medicine, Medical Univeristy of Bialystok

Bialystok, , Poland

Countries

Poland

Central Contacts

Agnieszka Adamska, Assoc.Prof.

Role: CONTACT

methyr@umb.edu.pl, agnieszka.adamska@umb.edu.pl

+48 85 746 86 07

Aldona Kowalska, Assoc.Prof.

Role: CONTACT

aldona.kowalska@onkol.kielce.pl

+48 41 36 74 181

Other Identifiers

2020/ABM/01/00100

Identifier Type: -

Identifier Source: org_study_id