Back to resultsStudy of Resistance to Thyroid Hormone After Long-term Exposure in People With Thyroid Cancer
Primary Purpose
Thyroid Cancer
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Thyrotropin Releasing Hormone (TRH)
levothyroxine
Hypothyroidism QOL questionnaire
Sponsored by
About this trial
This is an interventional diagnostic trial for Thyroid Cancer focused on measuring Thyrotropin Releasing Hormone (TRH), 20-079
Eligibility Criteria
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).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
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
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT04868045
First Posted
April 28, 2021
Last Updated
February 16, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT04868045
Brief Title
Study of Resistance to Thyroid Hormone After Long-term Exposure in People With Thyroid Cancer
Official Title
Evaluation of The Development of Central Resistance to Thyroid Hormone After Prolonged Exposure to Excess Thyroid Hormone in Thyroid Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of accrual
Study Start Date
April 27, 2021 (Actual)
Primary Completion Date
February 15, 2023 (Actual)
Study Completion Date
February 15, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Cancer
Keywords
Thyrotropin Releasing Hormone (TRH), 20-079
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
This is a prospective, single center, pilot study of the hypothalamic-pituitary-thyroid axis in adult patients with thyroid cancer.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patients with a history of thyroid hormone suppression (TSH<0.5 mU/L) for at least 5 years
Arm Type
Experimental
Arm Description
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.
Arm Title
Patients with no history of TSH suppression
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Thyrotropin Releasing Hormone (TRH)
Intervention Description
TRH administration will be given as a 200-mcg single IV bolus on Day 1 and Day 5.
Intervention Type
Drug
Intervention Name(s)
levothyroxine
Intervention Description
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
Other
Intervention Name(s)
Hypothyroidism QOL questionnaire
Intervention Description
Administer standardized Hypothyroidism QOL questionnaire.
Primary Outcome Measure Information:
Title
change in peak TSH levels
Description
in response to TRH stimulation between day 1 (baseline) and day 5 after three days of high dose LT3 treatment.
Time Frame
day 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie Fish, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center
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Study of Resistance to Thyroid Hormone After Long-term Exposure in People With Thyroid Cancer
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