Energy Metabolism in Thyroidectomized Patients

NCT04782856 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: HM200161691R21DK122310-01A1
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to measure the changes in energy metabolism (how the body burns energy), cardiovascular function (heart function), and lipid metabolism (cholesterol break down and building) before and after thyroidectomy (surgical removal of thyroid gland) in response to two approved therapies for hypothyroidism: levothyroxine (LT4) or Liothyronine/levothyroxine (LT3/LT4) combination therapy.

Conditions

Thyroid Goiter; Hypothyroidism; Thyroid Cancer

Outcome Measures

Primary Outcomes (3)

• Short Term Change in Weight

  Weight will be measured in kilograms using a stadiometer

  Baseline to 6 months post surgery

• Energy Expenditure (EE)

  24-hour EE will be measured using the whole room indirect calorimeter (WRIC) technique

  Baseline to 6 months

• Change in Cholesterol

  Cholesterol will be measured using a standard lipid panel.

  Baseline to 6 months post surgery

Other Outcomes (1)

• Change in Quality of Life

  Baseline to 6 months post surgery

Study Arms (2)

Single therapy

ACTIVE COMPARATOR

Levothyroxine (LT4) and placebo (a look-alike inactive substance, a "sugar pill") Patients in the LT4 group will be started at a dose of 1.6 mcg/Kg (52 The VCU Investigational Pharmacy will over-encapsulate LT4 plus placebo, in "AM" and "PM" color coded capsules. Patients will be instructed to take the AM drug first thing in the morning with water only, and to wait at least 30 minutes before taking other medications coffee or breakfast. The PM dose will be taken at least 30 minutes before dinner. Dose adjustments will be performed at the 6-week and 3-month follow up visits by an unblinded endocrinologist (Dr. Yavuz) aiming to achieve and maintain a target TSH within the normal range and within ± 0.5 mcIU/ml from the baseline (pre-surgery) TSH, Doses will be rounded to the nearest available formulation.

Drug: Levothyroxine; Drug: Placebo

Combination therapy

EXPERIMENTAL

Liothyronine/levothyroxine (LT3/LT4) combination therapy. LT4/LT3 group will have 25 mcg of LT4 substituted with 5 mcg LT3 twice daily, to mimic the average daily T3 production form the thyroid The VCU Investigational Pharmacy will over-encapsulate LT4 plus 5 mcg LT3 in "AM" and "PM" color coded capsules. Patients will be instructed to take the AM drug first thing in the morning with water only, and to wait at least 30 minutes before taking other medications coffee or breakfast. The PM dose will be taken at least 30 minutes before dinner. Dose adjustments will be performed at the 6-week and 3-month follow up visits by an unblinded endocrinologist (Dr. Yavuz) aiming to achieve and maintain a target TSH within the normal range and within ± 0.5 mcIU/ml from the baseline (pre-surgery) TSH, Doses will be rounded to the nearest available formulation. No changes will be made in LT3.

Drug: Levothyroxine; Drug: Liothyronine

Interventions

Levothyroxine DRUG

levothyroxine sodium tablet for oral use

Also known as: L-Thryroxine

Combination therapy; Single therapy

Liothyronine DRUG

Liothyronine sodium tablets for oral use treatment of hypothyroidism

Also known as: Cytomel

Combination therapy

Placebo DRUG

inert sugar tablets for oral use blinding for treatment of hypothyroidism

Also known as: Dextrose

Single therapy

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical indication for total thyroidectomy
• TSH at screening \>0.045\<4.5mlU/m
• Adult men and women Age ≥18-89 years of age
• Euthyroid patients with clinical indication for total thyroidectomy
• Indication to total thyroidectomy for benign goiter or thyroid cancer not requiring suppressive thyroid hormone therapy

You may not qualify if:

• Weight \<50 or \>150 Kg
• Graves' disease
• Use of thyroid hormone therapy or thyroid supplements (at screening) except for multinodular goiter
• Indication for thyroid hormone suppressive therapy following surgery
• Uncontrolled arterial hypertension stage 2 or greater (\>140/90 mm Hg at screening) while on medication (patients with hypertension controlled by therapy will be allowed to participate).
• Uncontrolled diabetes (HbA1c \> 8.% at screening or Fructosamine \> 325 mmol/L)
• History of cardiovascular disease, congestive heart failure or unstable coronary artery disease (angina, coronary event, or revascularization within 6 months); atrial fibrillation; or ventricular arrhythmia,
• History of major depression or psychosis
• Patients who are Pregnant, breastfeeding planned pregnancy within six months from the thyroidectomy
• Any conditions that in the opinion of the PI may impede the successful completion of the study

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Goiter; Hypothyroidism; Thyroid Neoplasms

Interventions

Thyroxine; Triiodothyronine; Glucose

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Thyronines; Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Francesco S. Celi, MD, MHSc.
• Organization: Uconn Health

celi@uchs.edu

860-679-2715

Study Officials

• Angeliki M Stamatouli, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 4, 2021
• Study Start: October 28, 2020
• Primary Completion: April 19, 2023
• Study Completion: April 19, 2023
• Last Updated: June 14, 2024
• Results First Posted: June 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)