Variations in the DIO2 and MCT10 Genes and Effect of Triiodothyronine Treatment

Longtime Effect of Combination Treatment With L-thyroxine (L-T4) and Liothyronine (L-T3) in Patients With Persistent Hypothyroid Symptoms - Relation to Polymorphisms (SNP) in the DIO2 and the MCT10 Gene

Hypothesis: Variations in the deiodinase 2 gene and monocarboxylate transporter 10 gene is associated with improvement in quality of life after initiation of combination therapy with L-Thyroxine and Liothyronine in patients with persistent hypothyroid symptoms despite conventional L-thyroxine mono-therapy.

Purpose: To re-test this hypothesis in patients with continued perceived effect of Liothyronine treatment at least one year after initiation in a patient population more representing of daily clinical practice. The study will help determine whether testing of specific gene variations might predict longtime effect of combination therapy.

Study Overview

• Status: Completed
• Conditions: Hypothyroidism

• Study Type: Observational
• Enrollment (Actual): 82

Contacts and Locations

• Study Contact: Name: Christian Z Jensen, MD; Phone Number: +45 52652688; Email: christian.zinck.jensen.01@regionh.dk

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients in this study have been diagnosed with hypothyroidism and have had persistent hypothyroid symptoms despite L-thyroxine mono-therapy. They have all been referred to the department of endocrinology and have been examined by a trained endocrinologist. All patients have at least one year before the study initiated combination therapy with L-thyroxine and Liothyronine.

Description

Inclusion Criteria:

• Patients admitted to the department of endocrinology with the diagnose hypothyroidism because of persistent hypothyroid symptoms despite treatment with L-thyroxine mono-therapy and normal and stable TSH (for at least 6 months).
• Started in combination therapy with L-thyroxine and Liothyronine in an approximately 17/1 ratio
• Exclusion of an alternative explanation for persistent hypothyroid symptoms

Exclusion Criteria:

• Initiation of L-thyroxine treatment in patients with s-TSH below upper normal limit (with assay in current use, that is TSH < 4 mU/L)
• Ongoing pregnancy
• Age below 18 years or above 80 years.
• Patients who do not read and understand information material given
• Patients who are not competent to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Responders; Patients in combination therapy due to persistent symptoms on L-thyroxin mono-therapy who experience a longtime effect of triiodothyronine treatment.
Non-responders; Patients who have tried combination therapy due to persistent symptoms on L-thyroxin mono-therapy, but did not experience a longtime effect.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymorphisms in DIO2/MCT10 and triiodothyronine treatment	Group 1(responders) and group 2(non-responders) are compared with regard to polymorphisms in the DIO2 gene and the MCT10 gene. Polymorphisms will be determined from DNA in a blood sample	Single assessment point, from 1-10 years after initiation of combination therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion treated with triiodothyronine	How many patients are treated with triiodothyronine at least one year after initiation of combination therapy.	Single assessment point, from 1-10 years after initiation of combination therapy
Quality of life questionnaire	Patients are scored on the ThyPRO questionnaire and a hypothyroid symptoms questionnaire.	Single assessment point, from 1-10 years after initiation of combination therapy
Who controls the treatment?	Patients report whether treatment is controlled by 1) a general practitioner 2) Patient self 3) other type of healthcare professional 4) a certified endocrinologist or 5) other	Single assessment point, from 1-10 years after initiation of combination therapy
How is current treatment controlled?	Patients report if current treatment is for example controlled by using blood samples or only on the basis of symptoms.	Single assessment point, from 1-10 years after initiation of combination therapy
Have therapy changed after the patient left the department of endocrinology?	Current hypothyroidism treatment and doses of medication	Single assessment point, from 1-10 years after initiation of combination therapy
TSH	Is the patient well regulated? Normal TSH: 0.1-4.0 (depending on assay used). Over-treatment: TSH < 0.1 (depending on assay used). Under-treatment: TSH>4 (depending on assay used).	Single assessment point, from 1-10 years after initiation of combination therapy
Osteoporosis	DXA-scan	Single assessment point, from 1-10 years after initiation of combination therapy
Risk of arrhythmia	Puls and blood pressure is measured. If arrhythmia is suspected, an ECG is performed.	Single assessment point, from 1-10 years after initiation of combination therapy

Collaborators and Investigators

• Sponsor: Birte Nygaard
• Investigators: Principal Investigator: Birte Nygaard, Ph.D., Herlev Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2019
• Primary Completion (Actual): August 1, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism
• Other Study ID Numbers: T3SNP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No