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

NCT04868045 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 20-079
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Keywords

Thyrotropin Releasing Hormone (TRH); 20-079

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

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

EXPERIMENTAL

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); Drug: levothyroxine; Other: Hypothyroidism QOL questionnaire

Patients with no history of TSH suppression

EXPERIMENTAL

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); Drug: levothyroxine; Other: Hypothyroidism QOL questionnaire

Interventions

Thyrotropin Releasing Hormone (TRH) DRUG

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

Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years; Patients with no history of TSH suppression

levothyroxine 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.

Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years; Patients with no history of TSH suppression

Hypothyroidism QOL questionnaire OTHER

Administer standardized Hypothyroidism QOL questionnaire.

Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years; Patients with no history of TSH suppression

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• patients with a history of thyroid hormone suppression (TSH\<0.5 mU/L) for at least 5 years
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

Thyrotropin-Releasing Hormone; Thyroxine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Thyroid Hormones; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Stephanie Fish, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: April 30, 2021
• Study Start: April 27, 2021
• Primary Completion: February 15, 2023
• Study Completion: February 15, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share