LEVOLIO: Combined Replacement Therapy With Levothyroxine and Liothyronine in Thyroidectomized Patients

Sponsor
Azienda USL Modena (Other)
Overall Status
Completed
CT.gov ID
NCT03053115
Collaborator
(none)
160
1
2
63.5
2.5

Study Details

Study Description

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
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
160 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 :
Mar 14, 2017
Actual Primary Completion Date :
Sep 5, 2021
Actual Study Completion Date :
Jun 30, 2022

Arms and Interventions

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

Primary Outcome Measures

  1. 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 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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [baseline and then repeated at 6, 12 weeks and 24 weeks]

    weight measurement

  2. height (cm) [baseline]

    height measurement

  3. Body composition [baseline and then repeated at 24 weeks]

    Bone Densitometry (DEXA) total body

  4. Bone composition [baseline and then repeated at 24 weeks]

    Bone Densitometry (DEXA) at lumbar spine and hip

  5. quality of life changes [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 [baseline and then repeated at 12 weeks and 24 weeks]

    change from baseline tissue specific miRNA expression at 12 and 24 weeks

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 AziendaUSLModena Modena Italy 41126

Sponsors and Collaborators

  • Azienda USL Modena

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Manuela Simoni, Director of the Unit of Endocrinology, Azienda USL Modena
ClinicalTrials.gov Identifier:
NCT03053115
Other Study ID Numbers:
  • EudraCT: 2016-000687-41
First Posted:
Feb 14, 2017
Last Update Posted:
Jul 28, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Manuela Simoni, Director of the Unit of Endocrinology, Azienda USL Modena
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 28, 2022