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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Thyroid Cancer
• Intervention / Treatment: Drug: Thyrotropin Releasing Hormone (TRH); Drug: levothyroxine; Other: Hypothyroidism QOL questionnaire

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: James Fagin, MD; Phone Number: 646-608-2921
      • Contact: Stephanie J. Fish, MD; Phone Number: 646-888-3274

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in peak TSH levels	in response to TRH stimulation between day 1 (baseline) and day 5 after three days of high dose LT3 treatment.	day 5

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): February 15, 2023
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): April 30, 2021

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Thyrotropin Releasing Hormone (TRH); 20-079
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones; Thyrotropin-Releasing Hormone
• Other Study ID Numbers: 20-079

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No