Energy Metabolism in Thyroidectomized Patients

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.

Study Overview

• Status: Completed
• Conditions: Hypothyroidism; Thyroid Cancer; Thyroid Goiter
• Intervention / Treatment: Drug: Levothyroxine; Drug: Placebo; Drug: Liothyronine

Detailed Description

In this study, Levothyroxine (LT4) and placebo (a look-alike inactive substance, a "sugar pill") will be compared to Liothyronine/ Levothyroxine (LT3/LT4) combination therapy.

Levothyroxine LT4 and Liothyronine (LT3) are drugs approved by the U. S. Food and Drug Administration (FDA).

All participants will be required follow VCU Health COVID-19 standard of Care screening procedures.

This study requires approximately five study visits The five-study visits required will be a Screening Visit (outpatient), one Baseline Visit, (inpatient) one Six Week Visit, (outpatient), one Three Month Visit and one Six Month Visit (both inpatient). A COVID-19 test will be done 48 hours (2 days) before each of the three-inpatient visit, Baseline Visit, Three Month and Six Month Visit.

Participants will be asked to:

1. Give permission for the researchers to collect information about their medical history from participants and their medical records five times during the study visits and for 5 years after the study visits.
2. Have a Physical exam done 5 times
3. 24-hour energy expenditure recording in the Whole room indirect calorimeter studies 3 times (inpatient overnight stays: Baseline, Three months, and Six months visits)
4. Study drug will be dispensed three times
5. Have study drug dose adjustments two times
6. Genomic blood draw for DNA one time
7. Have blood drawn five times
8. Have an DXA Scan two times
9. Have an Echocardiogram three times
10. Complete questionnaire three times
11. Have Accelerometers sensors laced 3 times (inpatient overnight stays: Baseline, Three months, and Six months visits)
12. ClearSight (blood pressure monitoring) procedure three times
13. Be randomized to take either Levothyroxine LT4 + placebo group or LevothyroxineLT3/Liothyronine LT4 group from baseline through 6 months

Participation in this study will last up to 6 months after surgery. Approximately 30 total individuals will participate in this study

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Weight <50 or >150 Kg
2. Graves' disease
3. Use of thyroid hormone therapy or thyroid supplements (at screening) except for multinodular goiter
4. Indication for thyroid hormone suppressive therapy following surgery
5. 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).
6. Uncontrolled diabetes (HbA1c > 8.% at screening or Fructosamine > 325 mmol/L)
7. 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,
8. History of major depression or psychosis
9. Patients who are Pregnant, breastfeeding planned pregnancy within six months from the thyroidectomy
10. Any conditions that in the opinion of the PI may impede the successful completion of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single therapy; 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; levothyroxine sodium tablet for oral use; Other Names: L-Thryroxine; Drug: Placebo; inert sugar tablets for oral use blinding for treatment of hypothyroidism; Other Names: Dextrose
Experimental: Combination therapy; 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; levothyroxine sodium tablet for oral use; Other Names: L-Thryroxine; Drug: Liothyronine; Liothyronine sodium tablets for oral use treatment of hypothyroidism; Other Names: Cytomel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life	ThyPRO-39, a thyroid specific quality of life instrument, was used to assess a participant's quality of life. ThyPRO-39 interrogates 12 individual domains and a composite on the 0 to 100 scale (0 best). A difference of 5 points corresponds to a small to moderate effect between two treatment arms. This outcome represents the change in score between when taken at baseline and then again at 6 months post surgery. The larger the increase in score, the better the improvement in the participant's quality of life. Each domain and the composite are being reported separately.	Baseline to 6 months post surgery

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Angeliki M Stamatouli, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Actual): April 19, 2023
• Study Completion (Actual): April 19, 2023

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Hypothyroidism; Thyroid Diseases; Goiter
• Other Study ID Numbers: HM20016169; 1R21DK122310-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No