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

Study Description

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Brief Summary:

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, measuring tissue markers levels, such as thyroid stimulating hormone(TSH), sex hormone binding globulin (SHBG), total cholesterol, LDL cholesterol, lipoprotein A, osteocalcin, urinary N-telopeptide, ferritin, myoglobin, creatine kinase, glucose 6 phosphate dehydrogenases, angiotensin-converting enzyme (ACE). The secondary endpoints are bone and metabolic modifications, evaluated by DEXA, quality of life, tissue specific miRNA expression, polymorphisms of genes involved in thyroid hormones metabolism.

Condition or disease	Intervention/treatment	Phase
Hypothyroidism	Drug: Liothyronine; Drug: Levothyroxin; Drug: Placebos	Phase 2; Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	260 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Combined Replacement Therapy With Levothyroxine and Liothyronine in Thyroidectomized Patients: Effects on Peripheral Tissues. A Prospective, Randomized, Controlled, Double-blind Study
Actual Study Start Date :	March 14, 2017
Estimated Primary Completion Date :	February 2019
Estimated Study Completion Date :	December 31, 2019

Arms and Interventions

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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

Outcome Measures

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Primary Outcome Measures :

1. 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)
2. 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)
3. 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)
4. 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)
5. 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)
6. change from baseline LDL 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 LDL cholesterol serum levels at 12 and 24 weeks (mg/dl)
7. change from baseline lipoprotein (a) serum levels at 12 and 24 weeks (mg/dl) [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
   change from baseline lipoprotein (a) serum levels at 12 and 24 weeks (mg/dl)
8. change from baseline urinary N-telopeptide levels at 12 and 24 weeks (nmol/mmol creatinine) [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
   change from baseline urinary N-telopeptide levels at 12 and 24 weeks (nmol/mmol creatinine)
9. change from baseline ferritin serum levels at 12 and 24 weeks (ng/ml) [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
   change from baseline ferritin serum levels at 12 and 24 weeks (ng/ml)
10. change from baseline myoglobin serum levels at 12 and 24 weeks (microgr/L) [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
    change from baseline myoglobin serum levels at 12 and 24 weeks (microgr/L)
11. change from baseline creatine kinase serum levels at 12 and 24 weeks (mU/mL) [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
    change from baseline creatine kinase serum levels at 12 and 24 weeks (mU/mL)
12. change from baseline glucose-6-phosphate dehydrogenases serum levels at 12 and 24 weeks (U/gHb) [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
    change from baseline glucose-6-phosphate dehydrogenases serum levels at 12 and 24 weeks (U/gHb)
13. change from baseline ACE serum levels at 12 and 24 weeks (mc/L) [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
    change from baseline ACE serum levels at 12 and 24 weeks (mc/L)

Secondary Outcome Measures :

1. weight (kg) [ Time Frame: baseline and then repeated at 6, 12 weeks and 24 weeks ]
   weight measurement
2. height (cm) [ Time Frame: baseline ]
   height measurement
3. Body composition [ Time Frame: baseline and then repeated at 24 weeks ]
   Bone Densitometry (DEXA) total body
4. Bone composition [ Time Frame: baseline and then repeated at 24 weeks ]
   Bone Densitometry (DEXA) at lumbar spine and hip
5. quality of life changes [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
   score at validated questionnaires
6. change from baseline tissue specific miRNA expression at 12 and 24 weeks [ Time Frame: baseline and then repeated at 12 weeks and 24 weeks ]
   change from baseline tissue specific miRNA expression at 12 and 24 weeks

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Italy
AziendaUSLModena	Recruiting
Modena, Italy, 41126
Contact: Manuela Simoni, MD, PhD 00390593961806 manuela.simoni@unimore.it
Principal Investigator: Manuela Simoni, MD, PhD

Sponsors and Collaborators

Azienda USL Modena

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Manuela Simoni, Director of the Unit of Endocrinology, Azienda USL Modena
ClinicalTrials.gov Identifier:	NCT03053115 History of Changes
Other Study ID Numbers:	EudraCT: 2016-000687-41
First Posted:	February 14, 2017
Last Update Posted:	March 21, 2017
Last Verified:	March 2017

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Hypothyroidism; Thyroid Diseases; Endocrine System Diseases