Can Levothyroxine Treatment Reduce the Development of Cardio-metabolic Disorder in Subclinical Hypothyroidism?

2. Aim/ Objectives The aim of this study is to evaluate the clinical, laboratory and echocardiographic findings in children with SCH.

To investigate the effect of replacement therapy with levothyroxine on cardiovascular risk factors in children with SCH.

Study Overview

• Status: Unknown
• Conditions: Subclinical hypothyroïdism
• Intervention / Treatment: Drug: Levothyroxine

Detailed Description

Sub-clinical hypothyroidism (SCH) is a form of thyroid dysfunction in which the thyroid-stimulating hormone (TSH) level is high, while serum total/free thyroxine (T4/fT4) is within the normal reference range . SCH is mostly detected accidentally as most of the patients manifest few or no signs of thyroid dysfunction.

The most common causative factor for SCH is chronic autoimmune thyroiditis characterized by high titers of thyroid peroxidase antibodies, thyroglobulin antibodies and rarely TSH receptor blocking antibodies. However, mutations in several proteins involving in TSH action including TSH receptor gene and mutations of dual oxidase 2 (DUOX2), phosphodiesterase 8B and thyroid peroxidase have also been demonstrated as causes of TSH elevation .

SCH might be associated with endothelial dysfunction due to early changes in proatherogenic profiles as there is elevation in plasma levels of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) in SCH patients , also there is increased risk of hypertension in SCH patients than in euthyroid .

Many studies found that homocysteine concentration appears to be increased in hypothyroidism and decreased in hyperthyroidism, and there is relationship between hyperhomocysteinemia and cardiovascular disease, including increased platelet aggregation, increased coagulation or reduced thrombolysis and endothelial dysfunction .

The acute-phase reactant hs-CRP is known to be a sensitive and non-specific marker for inflammation, tissue damage and infection . Serum hs-CRP measurements are used to determine cardiovascular risk. hs-CRP is regarded as a predictive marker for myocardial infarction, stroke, peripheral artery disease and sudden cardiac death .

The treatment of children with SCH is controversial; and there is not enough evidence that treatment can prevent the risk of developing cardiovascular and metabolic disorders in SCH.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Nashwa MOhamed Abd elwahab, MSCof pediatrics; Phone Number: 01061487888; Email: nashwa.abotaleb@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Patients aged from 5-15 years diagnosed with SH (patients with elevated TSH and normal Ft4 on two different measurements 4-6 weeks apart).

Exclusion Criteria:

• 1. Patients with acute or chronic disorders (anemia, infection, diabetes mellitus, malignancy, liver and renal disorder).

  2. Patients with a history of medication that affect thyroid function tests as glucocorticoids, dopamine or dobutamine, amiodarone, lithium, interferons, alemtuzumab.

  3. Patients with BMI>95 percentile.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group A; patiWill receive L-T4 treatment at a dose 1 µg/kg/day for 12 weeks. And the dose will be titrated every 4 weeksents with SCH will be subjected to clinical, laboratory and imaging assessment and	Drug: Levothyroxine; investigate the effect of replacement therapy with levothyroxine on cardiovascular risk factors in children with SCH.
No Intervention: Group B; .pWill not receive treatment.atients with SCH will be subjected to clinical, laboratory and imaging assessment and

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
: Normalization of TSH.	Normalization of TSH by receive L-T4 treatment at a dose 1 µg/kg/day for 12 weeks. And the dose will be titrated every 4 weeks then check differences in results between baseline assessment and12 weeks after intervention.	12 week

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): February 1, 2021

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism; Metabolic Diseases
• Other Study ID Numbers: Sub clinical hypothyroidism

Drug and device information, study documents

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