Study of Resistance to Thyroid Hormone After Long-term Exposure in People With Thyroid Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04868045

Collaborator

(none)

Enrollment

Location

Arms

23.1

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to find out whether people who have had thyroid cancer develop resistance to treatment with thyroid hormones after having received high doses of thyroid drugs for many years.

Condition or Disease	Intervention/Treatment	Phase
Thyroid Cancer	Drug: Thyrotropin Releasing Hormone (TRH) Drug: levothyroxine Other: Hypothyroidism QOL questionnaire	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a prospective, single center, pilot study of the hypothalamic-pituitary-thyroid axis in adult patients with thyroid cancer.This is a prospective, single center, pilot study of the hypothalamic-pituitary-thyroid axis in adult patients with thyroid cancer.

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Evaluation of The Development of Central Resistance to Thyroid Hormone After Prolonged Exposure to Excess Thyroid Hormone in Thyroid Cancer Patients

Actual Study Start Date :

Apr 27, 2021

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years Study subjects will be given 200mcg of TRH as a single intravenous (IV) bolus in endocrine clinic on Day 1 and Day 5. LT3 will be administered orally, twice a day (12 hours apart i.e. 8 AM and 8 PM) at a dosage of 10 mcg on Day 2-4. Levothyroxine will be taken after the TRH stimulation tests on Day 1 and day 5. Levothyroxine will be taken on Days 2-4 of the study. *Patients will take their own LT4 that they are prescribed by their endocrinologist. The dose of Levothyroxine is titrated for each patient.	Drug: Thyrotropin Releasing Hormone (TRH) TRH administration will be given as a 200-mcg single IV bolus on Day 1 and Day 5. Drug: levothyroxine Patients maintenance dose of levothyroxine will be taken throughout the study. On Day 1 and Day 5, the levothyroxine will be taken after the TRH test is complete. On Days 2- 4, the levothyroxine will be taken in the morning. Other: Hypothyroidism QOL questionnaire Administer standardized Hypothyroidism QOL questionnaire.
Experimental: Patients with no history of TSH suppression Study subjects will be given 200mcg of TRH as a single intravenous (IV) bolus in endocrine clinic on Day 1 and Day 5. LT3 will be administered orally, twice a day (12 hours apart i.e. 8 AM and 8 PM) at a dosage of 10 mcg on Day 2-4. Levothyroxine will be taken after the TRH stimulation tests on Day 1 and day 5. Levothyroxine will be taken on Days 2-4 of the study. *Patients will take their own LT4 that they are prescribed by their endocrinologist. The dose of Levothyroxine is titrated for each patient.	Drug: Thyrotropin Releasing Hormone (TRH) TRH administration will be given as a 200-mcg single IV bolus on Day 1 and Day 5. Drug: levothyroxine Patients maintenance dose of levothyroxine will be taken throughout the study. On Day 1 and Day 5, the levothyroxine will be taken after the TRH test is complete. On Days 2- 4, the levothyroxine will be taken in the morning. Other: Hypothyroidism QOL questionnaire Administer standardized Hypothyroidism QOL questionnaire.

Arm

Intervention/Treatment

Experimental: Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years

Study subjects will be given 200mcg of TRH as a single intravenous (IV) bolus in endocrine clinic on Day 1 and Day 5. LT3 will be administered orally, twice a day (12 hours apart i.e. 8 AM and 8 PM) at a dosage of 10 mcg on Day 2-4. Levothyroxine will be taken after the TRH stimulation tests on Day 1 and day 5. Levothyroxine will be taken on Days 2-4 of the study. *Patients will take their own LT4 that they are prescribed by their endocrinologist. The dose of Levothyroxine is titrated for each patient.

Drug: Thyrotropin Releasing Hormone (TRH)

TRH administration will be given as a 200-mcg single IV bolus on Day 1 and Day 5.

Drug: levothyroxine

Patients maintenance dose of levothyroxine will be taken throughout the study. On Day 1 and Day 5, the levothyroxine will be taken after the TRH test is complete. On Days 2- 4, the levothyroxine will be taken in the morning.

Other: Hypothyroidism QOL questionnaire

Administer standardized Hypothyroidism QOL questionnaire.

Experimental: Patients with no history of TSH suppression

Drug: Thyrotropin Releasing Hormone (TRH)

TRH administration will be given as a 200-mcg single IV bolus on Day 1 and Day 5.

Drug: levothyroxine

Other: Hypothyroidism QOL questionnaire

Administer standardized Hypothyroidism QOL questionnaire.

Outcome Measures

Primary Outcome Measures

change in peak TSH levels [day 5]
in response to TRH stimulation between day 1 (baseline) and day 5 after three days of high dose LT3 treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 or older
Due to a diagnosis of thyroid cancer based on pathology patient underwent a total thyroidectomy
No evidence of active disease based on routine surveillance testing showing no suspicious findings on neck ultrasound and low thyroglobulin levels (<1.0 ng/ml) with negative thyroglobulin antibodies within one year of study enrollment. For the study patients, this response can be evaluated after five years of TSH suppression. For control subjects, this response can be evaluated after two years of surveillance.
Two groups:
8 patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years
8 patients with no history of TSH suppression
Normal TSH level based on the laboratory reference range for at least 6 months at the time of study enrollment.
Blood pressure range of >90/60 and <180/100. Patients may be included in the study if blood pressure has been treated with medication and normalized.

Exclusion Criteria:

Patient reported history of symptomatic heart disease including unstable angina or NYHA stage III or IV heart failure.
Patient reported history of one of the following cardiac arrhythmias: atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular fibrillation, or ventricular tachycardia.
Patient reported history of uncontrolled hypotension (<90/60) or hypertension (>180/100).
History of renal dysfunction with creatinine more than 1.5 times the upper limit of normal based on recent laboratory testing
Known hypersensitivity to the drug
Pregnant or breast feeding
Prior history of seizures or brain damage
Patients on chronic therapy with levodopa
Patients on therapeutic doses of acetylsalicylic acid (2 - 3.6 gm/day)
Patients with conditions that result in disruption of the hypothalamic-pituitary axis (i.e. hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation, or head trauma).