Combined Replacement Therapy With Levothyroxine and Liothyronine in Thyroidectomized Patients (LEVOLIO)

April 19, 2023 updated by: Manuela Simoni, Azienda USL Modena

Combined Replacement Therapy With Levothyroxine and Liothyronine in Thyroidectomized Patients: Effects on Peripheral Tissues. A Prospective, Randomized, Controlled, Double-blind Study

The aim of the study is to evaluate the peripheral tissue response to the combined administration of levothyroxine (LT4) and liothyronine (LT3) in hypothyroid patients with residual thyroid function virtually absent (thyroidectomized). Cases will be treated with LT4+LT3, at personalized doses according to clinical guidelines and respecting the circadian rhythmicity of LT3 and the physiological T3/T4 ratio. Controls will be treated with LT4 and placebo. Treatment duration: 24 weeks.

The primary endpoint will be the peripheral effect of thyroid hormones. The secondary endpoints are bone and metabolic modifications, and changes in quality of life. Moreover any changes of outcomes related to polymorphisms of genes involved in thyroid hormones metabolism will be evaluated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Modena, Italy, 41126
        • AziendaUSLModena

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • older than 18 years
  • capable of consent
  • able to fill in a questionnaire in italian
  • thyroidectomized
  • serum thyroglobulin levels below 0.2 ng/ml and antibodies anti-thyroglobulin undetectable (below normal range)
  • well treated taking stable doses of levothyroxine in tablets, in the previous 3 months

Exclusion Criteria:

  • TSH suppressive therapy
  • pregnancy
  • cardiac arrhythmias
  • severe liver, kidney or bone diseases
  • ongoing steroids treatment
  • ongoing or in the previous 12 months treatment with bone anti-resorptive, amiodarone, colestyramine or iron.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CASES
treatment with levothyroxine and liothyronine
Drug: Liothyronine
Cases will take liothyronine drops in the morning and two hours after dinner
Drug: Levothyroxin
Both cases and controls will take levothyroxine in the morning (entire dose for controls, reduced dose for cases)
Active Comparator: CONTROLS
treatment with levothyroxine and placebo
Drug: Levothyroxin
Both cases and controls will take levothyroxine in the morning (entire dose for controls, reduced dose for cases)
Drug: Placebos
Controls will take placebo two hours after dinner

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change from baseline SHBG serum levels at 12 and 24 weeks (nmol/L)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline SHBG serum levels at 12 and 24 weeks (nmol/L)
baseline and then repeated at 12 weeks and 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change from baseline TSH serum levels at 12 and 24 weeks (microIU/ml)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline TSH serum levels at 12 and 24 weeks (microIU/ml)
baseline and then repeated at 12 weeks and 24 weeks
change from baseline free triiodothyronine (fT3) serum levels at 12 and 24 weeks (pmol/L)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline free triiodothyronine (fT3) serum levels at 12 and 24 weeks (pmol/L)
baseline and then repeated at 12 weeks and 24 weeks
change from baseline free levothyroxine (fT4) serum levels at 12 and 24 weeks (pmol/L)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline free levothyroxine (fT4) serum levels at 12 and 24 weeks (pmol/L)
baseline and then repeated at 12 weeks and 24 weeks
change from baseline total cholesterol serum levels at 12 and 24 weeks (mg/dl)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline total cholesterol serum levels at 12 and 24 weeks (mg/dl)
baseline and then repeated at 12 weeks and 24 weeks
quality of life changes
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
score at validated questionnaires
baseline and then repeated at 12 weeks and 24 weeks
change from baseline HDL cholesterol serum levels at 12 and 24 weeks (mg/dl)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline HDL cholesterol serum levels at 12 and 24 weeks (mg/dl)
baseline and then repeated at 12 weeks and 24 weeks
change from baseline triglycerides serum levels at 12 and 24 weeks (mg/dl)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline triglycerides serum levels at 12 and 24 weeks (mg/dl)
baseline and then repeated at 12 weeks and 24 weeks
change from baseline C-terminal telopeptide of type 1 collagen at 12 and 24 weeks (ng/dl)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline C-terminal telopeptide of type 1 collagen at 12 and 24 weeks (ng/dl)
baseline and then repeated at 12 weeks and 24 weeks
change from baseline Bone alkaline phosphatase at 12 and 24 weeks (µg/L)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline Bone alkaline phosphatase at 12 and 24 weeks (µg/L)
baseline and then repeated at 12 weeks and 24 weeks
change from baseline Osteocalcin at 12 and 24 weeks (ng/mL)
Time Frame: baseline and then repeated at 12 weeks and 24 weeks
change from baseline Osteocalcin at 12 and 24 weeks (ng/mL)
baseline and then repeated at 12 weeks and 24 weeks
BMI (kg/m2)
Time Frame: baseline and then repeated at 6, 12 weeks and 24 weeks
body mass index
baseline and then repeated at 6, 12 weeks and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda USL Modena

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 14, 2017

Primary Completion (Actual)

September 5, 2021

Study Completion (Actual)

June 30, 2022

Study Registration Dates

First Submitted

November 25, 2016

First Submitted That Met QC Criteria

February 10, 2017

First Posted (Actual)

February 14, 2017

Study Record Updates

Last Update Posted (Actual)

April 21, 2023

Last Update Submitted That Met QC Criteria

April 19, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT: 2016-000687-41

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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