Combined Replacement Therapy With Levothyroxine and Liothyronine in Thyroidectomized Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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Hypothyroidism

Intervention / Treatment
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* Drug: Liothyronine
* Drug: Levothyroxin
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline SHBG serum levels at 12 and 24 weeks (nmol/L) | 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 |
| --- | --- | --- |
| BMI (kg/m2) | body mass index | baseline and then repeated at 6, 12 weeks and 24 weeks | 
| quality of life changes | score at validated questionnaires | baseline and then repeated at 12 weeks and 24 weeks | 
| change from baseline TSH serum levels at 12 and 24 weeks (microIU/ml) | 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) | 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) | 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) | change from baseline total cholesterol serum levels at 12 and 24 weeks (mg/dl) | baseline and then repeated at 12 weeks and 24 weeks | 
| change from baseline HDL cholesterol serum levels at 12 and 24 weeks (mg/dl) | 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) | 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) | 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 Osteocalcin at 12 and 24 weeks (ng/mL) | change from baseline Osteocalcin at 12 and 24 weeks (ng/mL) | baseline and then repeated at 12 weeks and 24 weeks | 
| change from baseline Bone alkaline phosphatase at 12 and 24 weeks (µg/L) | change from baseline Bone alkaline phosphatase at 12 and 24 weeks (µg/L) | baseline and then repeated at 12 weeks and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thyroid, levothyroxine, combined therapy