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

NCT ID: NCT04868045

Last Updated: 2023-02-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-27
• Study Completion Date: 2023-02-15

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.

Conditions

Thyroid Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Thyrotropin Releasing Hormone (TRH)

Intervention Type: DRUG

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

levothyroxine

Intervention Type: DRUG

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.

Hypothyroidism QOL questionnaire

Intervention Type: OTHER

Administer standardized Hypothyroidism QOL questionnaire.

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.

Group Type: EXPERIMENTAL

Thyrotropin Releasing Hormone (TRH)

Intervention Type: DRUG

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

levothyroxine

Intervention Type: DRUG

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.

Hypothyroidism QOL questionnaire

Intervention Type: OTHER

Administer standardized Hypothyroidism QOL questionnaire.

Interventions

Thyrotropin Releasing Hormone (TRH)

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

Intervention Type: 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.

Intervention Type: DRUG

Hypothyroidism QOL questionnaire

Administer standardized Hypothyroidism QOL questionnaire.

Intervention Type: OTHER

Eligibility Criteria

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.

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie Fish, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Related Links

http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

20-079

Identifier Type: -

Identifier Source: org_study_id