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

Phase 1

Withdrawn

• Conditions: Thyroid Cancer
• Interventions: Drug: Thyrotropin Releasing Hormone (TRH); Drug: levothyroxine; Other: Hypothyroidism QOL questionnaire

• Registration Number: NCT04868045
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-27
• Study First Submitted: 2021-04-28
• Study First Submitted QC: 2021-04-29
• Study First Posted: 2021-04-30
• Status Verified: 2023-02
• Primary Completion: 2023-02-15
• Study Completion: 2023-02-15
• Last Update Submitted: 2023-02-16
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Age 18 or older

• Due to a diagnosis of thyroid cancer, patient underwent a total thyroidectomy based on pathology.

• 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.

Read More

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).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years	Hypothyroidism QOL questionnaire	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.
Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years	Thyrotropin Releasing Hormone (TRH)	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.
Patients with no history of TSH suppression	Hypothyroidism QOL questionnaire	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.
Patients with no history of TSH suppression	Thyrotropin Releasing Hormone (TRH)	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.
Patients with no history of TSH suppression	levothyroxine	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.
Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years	levothyroxine	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.

Primary Outcome Measures

Name	Time	Method
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.