Thyroid Goiter, Hypothyroidism, Thyroid Cancer
Conditions
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.
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
Interventions
DRUGLevothyroxine
levothyroxine sodium tablet for oral use
DRUGLiothyronine
Liothyronine sodium tablets for oral use treatment of hypothyroidism
DRUGPlacebo
inert sugar tablets for oral use blinding for treatment of hypothyroidism
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short Term Change in Weight | Baseline to 6 months post surgery | Weight will be measured in kilograms using a stadiometer |
| Energy Expenditure (EE) | Baseline to 6 months | 24-hour EE will be measured using the whole room indirect calorimeter (WRIC) technique |
| Change in Cholesterol | Baseline to 6 months post surgery | Cholesterol will be measured using a standard lipid panel. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life | Baseline to 6 months post surgery | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Levothyroxine: levothyroxine sodium tablet for oral use
Placebo: inert sugar tablets for oral use blinding for treatment of hypothyroidism | 7 |
| 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.
Levothyroxine: levothyroxine sodium tablet for oral use
Liothyronine: Liothyronine sodium tablets for oral use treatment of hypothyroidism | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Single Therapy | Combination Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 9 Participants |
| Region of Enrollment United States | 7 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 0 / 7 | 1 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Change in Cholesterol
Cholesterol will be measured using a standard lipid panel.
Time frame: Baseline to 6 months post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Therapy | Change in Cholesterol | 43 mg/dL | Standard Deviation 73 |
| Combination Therapy | Change in Cholesterol | -35 mg/dL | Standard Deviation 52 |
Primary
Energy Expenditure (EE)
24-hour EE will be measured using the whole room indirect calorimeter (WRIC) technique
Time frame: Baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Therapy | Energy Expenditure (EE) | -39 calorie over 24 hours | Standard Deviation 68 |
| Combination Therapy | Energy Expenditure (EE) | 25 calorie over 24 hours | Standard Deviation 29 |
Primary
Short Term Change in Weight
Weight will be measured in kilograms using a stadiometer
Time frame: Baseline to 6 months post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Therapy | Short Term Change in Weight | 1.7 Kilogram | Standard Deviation 3.9 |
| Combination Therapy | Short Term Change in Weight | -0.76 Kilogram | Standard Deviation 2.1 |
Other Pre-specified
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.
Time frame: Baseline to 6 months post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Therapy | Change in Quality of Life | Domain: Eye | 13.1 score on a scale | Standard Deviation 17.3 |
| Single Therapy | Change in Quality of Life | Domain: Tiredness | 11.2 score on a scale | Standard Deviation 19.3 |
| Single Therapy | Change in Quality of Life | Domain: Social life | 9.5 score on a scale | Standard Deviation 14 |
| Single Therapy | Change in Quality of Life | Domain: Cognitive | 14.3 score on a scale | Standard Deviation 15.8 |
| Single Therapy | Change in Quality of Life | Domain: Anxiety | 14.3 score on a scale | Standard Deviation 19.1 |
| Single Therapy | Change in Quality of Life | Domain: Daily life | 7.14 score on a scale | Standard Deviation 13.1 |
| Single Therapy | Change in Quality of Life | Domain: Depressivity | 2.3 score on a scale | Standard Deviation 11.5 |
| Single Therapy | Change in Quality of Life | Composite | 14.3 score on a scale | Standard Deviation 28.3 |
| Single Therapy | Change in Quality of Life | Domain: Emotional | 9.5 score on a scale | Standard Deviation 18.9 |
| Single Therapy | Change in Quality of Life | Domain: Goiter | 23.8 score on a scale | Standard Deviation 36.8 |
| Single Therapy | Change in Quality of Life | Domain: Hyperthyroid | 12.5 score on a scale | Standard Deviation 20.4 |
| Single Therapy | Change in Quality of Life | Domain: Appearance | 9.5 score on a scale | Standard Deviation 47.2 |
| Single Therapy | Change in Quality of Life | Domain: Hypothyroid | -2.7 score on a scale | Standard Deviation 17.2 |
| Combination Therapy | Change in Quality of Life | Domain: Appearance | 38.3 score on a scale | Standard Deviation 62.8 |
| Combination Therapy | Change in Quality of Life | Domain: Goiter | 45 score on a scale | Standard Deviation 38 |
| Combination Therapy | Change in Quality of Life | Domain: Hypothyroid | 10 score on a scale | Standard Deviation 24 |
| Combination Therapy | Change in Quality of Life | Domain: Cognitive | 33.3 score on a scale | Standard Deviation 45.3 |
| Combination Therapy | Change in Quality of Life | Domain: Emotional | 40 score on a scale | Standard Deviation 41.8 |
| Combination Therapy | Change in Quality of Life | Domain: Hyperthyroid | 15 score on a scale | Standard Deviation 18.1 |
| Combination Therapy | Change in Quality of Life | Domain: Eye | 5 score on a scale | Standard Deviation 12.6 |
| Combination Therapy | Change in Quality of Life | Domain: Tiredness | 36.7 score on a scale | Standard Deviation 45.1 |
| Combination Therapy | Change in Quality of Life | Domain: Anxiety | 41.7 score on a scale | Standard Deviation 45.2 |
| Combination Therapy | Change in Quality of Life | Domain: Depressivity | 30 score on a scale | Standard Deviation 42.3 |
| Combination Therapy | Change in Quality of Life | Domain: Social life | 25 score on a scale | Standard Deviation 34.4 |
| Combination Therapy | Change in Quality of Life | Domain: Daily life | 38.3 score on a scale | Standard Deviation 51.2 |
| Combination Therapy | Change in Quality of Life | Composite | 45 score on a scale | Standard Deviation 64.7 |