Malignant Struma OvariiNCT01441154
Metabolic Effects of Synthetic Thyroid Hormone for Thyroid Cancer Treatment
An observational study of Malignant Struma Ovarii and Papillary Thyroid Cancer, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: Thyroid hormone is produced by the thyroid gland, an organ at the base of the neck. Thyroid hormone controls the body's metabolism and the function of many organs. The thyroid gland produces two forms of thyroid hormone: T4 and T3. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Malignant Struma Ovarii, Papillary Thyroid Cancer, Hurthle Cell Thyroid Cancer
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Sep 2011to 12 Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: primary clinical
Who may be able to join
- Subjects will be adult volunteers older than age 18 who underwent total thyroidectomy for the treatment of differentiated thyroid cancer, previously undergone radioactive iodine ablation of the thyroid gland remnant, with clinical indication for withdrawal from thyroid hormone replacement therapy in preparation for nuclear medicine imaging or therapeutic procedures with radioactive iodine. The patient population will be recruited from the participants in the 77-DK-0096 natural history protocol: Studies on Thyroid Nodules and Thyroid Cancer , PI Dr.Joanna Klubo-Gwiezdzinska and from the 10-C-0102 natural history protocol: Clinical and Genetic Studies in Familial Non-Medullary Thyroid Cancer , PI Electron Kebebew.
Who cannot join
- Significant thyroid residual greater than 5 gm as measure by ultrasound or greater than 5 percent uptake at 24 H on (123) I pre-treatment thyroid scan.
- Renal insufficiency or estimated creatinine clearance less than or equal to 60 mL/min/1.73M(2) BSA by MDRD equation before thyroid hormone withdrawal.
- Liver disease or ALT >2.5 times the upper laboratory reference limit.
- Pharmacologic therapy for the treatment of psychiatric conditions.
- History of, and/or current coronary artery disease.
- Current history or symptoms compatible with psychosis or major depression (including history of hospitalization for depression, history of attempted suicide, history of suicidal ideation). Use of antipsychotic medications.
Show all 14Show fewer
- History of drug or alcohol abuse within the last year; current use of illicit drugs or alcohol abuse (CAGE>3).
- Pregnancy (women of child-bearing potential must have a negative pregnancy test prior to inclusion) or use of hormonal contraceptives.
- Known allergy to L-T3.
- Current use of prescription medication or certain non-prescription medications and dietary supplements known to affect thyroid function and/or metabolism, or alter the pharmacokinetics of L-T3.
- Inability or unwillingness to follow the low-iodine, metabolic diet or non-compliance to the L-T3 administration regimen.
- The presence of persistent diarrhea or malabsorption syndromes that would interfere with the patient s ability to adequately absorb drugs.
- Inability to obtain venous access for sample collection, or basal hemoglobin of less than or equal to 10 g/dL.
- Low functional status (ECOG Performance Status > 2)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pharmacokinetic and Pharmacodynamic Studies of Liothyronine. A Study on the Metabolic Effects of Thyroid Hormone
Background:
- Thyroid hormone is produced by the thyroid gland, an organ at the base of the neck. Thyroid hormone controls the body's metabolism and the function of many organs. The thyroid gland produces two forms of thyroid hormone: T4 and T3. People who have thyroid cancer are treated with thyroid hormone therapy (synthetic T4, levothyroxine), which at times needs to be stopped to allow for cancer treatments. At these times, a different form of thyroid hormone (synthetic T3, liothyronine) is used to reduce the symptoms caused by low levels of thyroid hormone. Researchers want to know more about how changes in T3 hormone affect the body and organ function.
Read more
Objectives:
- To study how changes in T3 hormone levels affect the body and organ function.
Eligibility:
- Individuals at least 18 years of age who have had most or all of their thyroid removed to treat thyroid cancer who need to stop taking their regular thyroid hormone dose in preparation for the treatment of thyroid cancer.
Design:
- The study involves a screening visit and a baseline evaluation. It also includes an 11-day inpatient hospital stay.
- Participants will be screened with a physical exam and medical history. They will also have blood tests and a neck ultrasound.
- Participants will be evaluated with a physical exam, blood tests, and the following procedures:
- Glucose tolerance test to measure blood sugar
- Tests of body fat, muscle strength, and calorie burning levels
- Imaging studies of the heart, liver, and thigh muscles
- Quality of life questionnaires
- Food preference and diet questionnaires
- After 4 weeks of treatment with T3 hormone, participants will have an 11-day inpatient hospital stay to study the effect of thyroid hormone on their metabolism. The stay will involve the same tests done in the baseline evaluation.
Read the detailed description
In human adults thyroid hormone action plays a critical role in the modulation of metabolism and the function of virtually all organ/systems. The specificity of the hormonal action is ultimately the result of the interaction of the active hormone, triiodothyronine (T3), with the receptors isoforms and the co-activators and co-repressors specific for the various cells target of the hormonal action. Circulating and tissue levels of T3 are the result of the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, the peripheral conversion of T4 into T3, and the degradation of these hormones. This complex system has only been partially studied in humans and very little is known regarding the kinetics of T3, and in particular on the correlation between circulating levels of T3 and end-organ target tissue thyroid hormone action.
The aim of this protocol is to characterize the pharmacokinetics of T3 and its biological effects at various concentrations in a cohort of thyroidectomized patients undergoing thyroid hormone replacement therapy withdrawal for the management of thyroid cancer.
Sixteen patients with a clinical indication for thyroid hormone withdrawal in preparation for 131I therapy or 123I diagnostic scan for follow-up and management of differentiated thyroid cancer will be recruited for this study. After enrollment in the study, the patients baseline characteristics will be determined during an outpatient visit while receiving levothyroxine (L-T4) therapy. The L-T4 therapy then will be suspended and substituted with an equivalent thrice daily liothyronine (L-T3) therapy for one month. Patients will be admitted to the NIH Clinical Center on the day prior to withdrawal of the T3 therapy until the diagnostic scan or the administration of radioactive iodine. During the hospitalization for this research protocol, which is expected to last eleven days, the following studies will be performed: serial blood sampling for circulating thyroid hormones to obtain pharmacokinetic parameters of L-T3, lipids, glucose and insulin, resting energy expenditure, echocardiogram, skeletal muscle strength measurement, cardiac, hepatic and skeletal muscles MRI, and quality of life and well-being questionnaires. The pharmacokinetic parameters of L-T3 will also be assessed with the first dose after the diagnostic scan or the administration of radioactive iodine.
The results obtained from this study will help in understanding the effects of thyroid hormone on metabolism, and may lead to important information on how to optimize the duration of the thyroid hormone therapy withdrawal for the treatment of thyroid cancer.
- Conditions
- Malignant Struma Ovarii, Papillary Thyroid Cancer, Hurthle Cell Thyroid Cancer, Follicular Thyroid Cancer, Tall Cell Variant Thyroid Cancer
- Keywords
- Hypothyroidism, Thyroid Cancer, Triiodothyronine (T3), Energy Expenditure, Thyroid Hormone
- Medical subject headings
- Thyroid Cancer, Papillary, Thyroid cancer, Hurthle cell, Adenocarcinoma, Follicular, Hypothyroidism, Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Adults with clinical indication for withdrawal from thyroid hormone replacement therapy in preparation for nuclear medicine imaging or therapeutic procedures with radioactive iodine |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. To assess the pharmacokinetics of T3 in patients devoid of endogenous or exogenous T4 during acute L-T3 withdrawal at steady- state and after the first L-T3 dose administration
to study T3 kinetics in thyroidectomized patients treated with liothyronine (L- T3) replacement therapy in preparation for diagnostic or therapeutic nuclear medicine procedures for the follow-up and management of differentiated thyroid cancer
Measured: 4 weeks after stopping L-T4 thyroid hormone replacement therapy and starting L-T3 treatment
2. To estimate the minimal duration of L-T3 therapy withdrawal required to achieve a serum TSH level, equal or greater than 30 uIU/mL, to assure effective 131I therapy for treatment of differentiated thyroid cancer
to study T3 kinetics in thyroidectomized patients treated with liothyronine (L- T3) replacement therapy in preparation for diagnostic or therapeutic nuclear medicine procedures for the follow-up and management of differentiated thyroid cancer
Measured: 4 weeks after stopping L-T4 thyroid hormone replacement therapy and starting L-T3 treatment
3. To correlate clinical and biochemical parameters of thyroid hormone action, with circulating levels of T3 during L-T3 therapy withdrawal
to study T3 kinetics in thyroidectomized patients treated with liothyronine (L- T3) replacement therapy in preparation for diagnostic or therapeutic nuclear medicine procedures for the follow-up and management of differentiated thyroid cancer
Measured: 4 weeks after stopping L-T4 thyroid hormone replacement therapy and starting L-T3 treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2011 (estimated)
- Study start20 Sep 2011
- Primary completion12 Dec 2013
- Study completion12 Dec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malignant Struma OvariiStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kong Y Chen, Ph.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01441154
- Sponsor's protocol ID
- 110256
- Other IDs
- 11-DK-0256
- Status last verified
- Sep 2020
- First submitted
- 24 Sep 2011
- Last updated
- 28 Sep 2020
- Results posted
- No
Publications
Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097.
PubMed 11427693Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev. 2002 Feb;23(1):38-89. doi: 10.1210/edrv.23.1.0455.
PubMed 11844744Nguyen TT, DiStefano JJ 3rd, Yamada H, Yen YM. Steady state organ distribution and metabolism of thyroxine and 3,5,3'-triiodothyronine in intestines, liver, kidneys, blood, and residual carcass of the rat in vivo. Endocrinology. 1993 Dec;133(6):2973-83. doi: 10.1210/endo.133.6.8243325.
PubMed 8243325
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic and Pharmacodynamic Studies of Liothyronine. A Study on the Metabolic Effects of Thyroid Hormone
- ClinicalTrials.gov ID
- NCT01441154
- Acronym / sponsor ID
- 110256
- Conditions
- Malignant Struma Ovarii, Papillary Thyroid Cancer, Hurthle Cell Thyroid Cancer, Follicular Thyroid Cancer, Tall Cell Variant Thyroid Cancer
- Keywords
- Hypothyroidism, Thyroid Cancer, Triiodothyronine (T3), Energy Expenditure, Thyroid Hormone
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 20 Sep 2011 (actual)
- Primary completion
- 12 Dec 2013 (actual)
- Study completion
- 12 Dec 2013 (actual)
- First posted
- 27 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Thyroid hormone is produced by the thyroid gland, an organ at the base of the neck. Thyroid hormone controls the body's metabolism and the function of many organs. The thyroid gland produces two forms of thyroid hormone: T4 and T3. People who have thyroid cancer are treated with thyroid hormone therapy (synthetic T4, levothyroxine), which at times needs to be stopped to allow for cancer treatments. At these times, a different form of thyroid hormone (synthetic T3, liothyronine) is used to reduce the symptoms caused by low levels of thyroid hormone. Researchers want to know more about how changes in T3 hormone affect the body and organ function.
Objectives:
- To study how changes in T3 hormone levels affect the body and organ function.
Eligibility:
- Individuals at least 18 years of age who have had most or all of their thyroid removed to treat thyroid cancer who need to stop taking their regular thyroid hormone dose in preparation for the treatment of thyroid cancer.
Design:
- The study involves a screening visit and a baseline evaluation. It also includes an 11-day inpatient hospital stay.
- Participants will be screened with a physical exam and medical history. They will also have blood tests and a neck ultrasound.
- Participants will be evaluated with a physical exam, blood tests, and the following procedures:
- Glucose tolerance test to measure blood sugar
- Tests of body fat, muscle strength, and calorie burning levels
- Imaging studies of the heart, liver, and thigh muscles
- Quality of life questionnaires
- Food preference and diet questionnaires
- After 4 weeks of treatment with T3 hormone, participants will have an 11-day inpatient hospital stay to study the effect of thyroid hormone on their metabolism. The stay will involve the same tests done in the baseline evaluation.
Detailed description
In human adults thyroid hormone action plays a critical role in the modulation of metabolism and the function of virtually all organ/systems. The specificity of the hormonal action is ultimately the result of the interaction of the active hormone, triiodothyronine (T3), with the receptors isoforms and the co-activators and co-repressors specific for the various cells target of the hormonal action. Circulating and tissue levels of T3 are the result of the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, the peripheral conversion of T4 into T3, and the degradation of these hormones. This complex system has only been partially studied in humans and very little is known regarding the kinetics of T3, and in particular on the correlation between circulating levels of T3 and end-organ target tissue thyroid hormone action.
The aim of this protocol is to characterize the pharmacokinetics of T3 and its biological effects at various concentrations in a cohort of thyroidectomized patients undergoing thyroid hormone replacement therapy withdrawal for the management of thyroid cancer.
Sixteen patients with a clinical indication for thyroid hormone withdrawal in preparation for 131I therapy or 123I diagnostic scan for follow-up and management of differentiated thyroid cancer will be recruited for this study. After enrollment in the study, the patients baseline characteristics will be determined during an outpatient visit while receiving levothyroxine (L-T4) therapy. The L-T4 therapy then will be suspended and substituted with an equivalent thrice daily liothyronine (L-T3) therapy for one month. Patients will be admitted to the NIH Clinical Center on the day prior to withdrawal of the T3 therapy until the diagnostic scan or the administration of radioactive iodine. During the hospitalization for this research protocol, which is expected to last eleven days, the following studies will be performed: serial blood sampling for circulating thyroid hormones to obtain pharmacokinetic parameters of L-T3, lipids, glucose and insulin, resting energy expenditure, echocardiogram, skeletal muscle strength measurement, cardiac, hepatic and skeletal muscles MRI, and quality of life and well-being questionnaires. The pharmacokinetic parameters of L-T3 will also be assessed with the first dose after the diagnostic scan or the administration of radioactive iodine.
The results obtained from this study will help in understanding the effects of thyroid hormone on metabolism, and may lead to important information on how to optimize the duration of the thyroid hormone therapy withdrawal for the treatment of thyroid cancer.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –Adults with clinical indication for withdrawal from thyroid hormone replacement therapy in preparation for nuclear medicine imaging or therapeutic procedures with radioactive iodine |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- primary clinical
Key inclusion criteria (1 listed)
- Subjects will be adult volunteers older than age 18 who underwent total thyroidectomy for the treatment of differentiated thyroid cancer, previously undergone radioactive iodine ablation of the thyroid gland remnant, with clinical indication for withdrawal from thyroid hormone replacement therapy in preparation for nuclear medicine imaging or therapeutic procedures with radioactive iodine. The patient population will be recruited from the participants in the 77-DK-0096 natural history protocol: Studies on Thyroid Nodules and Thyroid Cancer , PI Dr.Joanna Klubo-Gwiezdzinska and from the 10-C-0102 natural history protocol: Clinical and Genetic Studies in Familial Non-Medullary Thyroid Cancer , PI Electron Kebebew.
Key exclusion criteria (14 listed)
- Significant thyroid residual greater than 5 gm as measure by ultrasound or greater than 5 percent uptake at 24 H on (123) I pre-treatment thyroid scan.
- Renal insufficiency or estimated creatinine clearance less than or equal to 60 mL/min/1.73M(2) BSA by MDRD equation before thyroid hormone withdrawal.
- Liver disease or ALT >2.5 times the upper laboratory reference limit.
- Pharmacologic therapy for the treatment of psychiatric conditions.
- History of, and/or current coronary artery disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
1. To assess the pharmacokinetics of T3 in patients devoid of endogenous or exogenous T4 during acute L-T3 withdrawal at steady- state and after the first L-T3 dose administration
Time frame: 4 weeks after stopping L-T4 thyroid hormone replacement therapy and starting L-T3 treatment
to study T3 kinetics in thyroidectomized patients treated with liothyronine (L- T3) replacement therapy in preparation for diagnostic or therapeutic nuclear medicine procedures for the follow-up and management of differentiated thyroid cancer
2. To estimate the minimal duration of L-T3 therapy withdrawal required to achieve a serum TSH level, equal or greater than 30 uIU/mL, to assure effective 131I therapy for treatment of differentiated thyroid cancer
Time frame: 4 weeks after stopping L-T4 thyroid hormone replacement therapy and starting L-T3 treatment
to study T3 kinetics in thyroidectomized patients treated with liothyronine (L- T3) replacement therapy in preparation for diagnostic or therapeutic nuclear medicine procedures for the follow-up and management of differentiated thyroid cancer
3. To correlate clinical and biochemical parameters of thyroid hormone action, with circulating levels of T3 during L-T3 therapy withdrawal
Time frame: 4 weeks after stopping L-T4 thyroid hormone replacement therapy and starting L-T3 treatment
to study T3 kinetics in thyroidectomized patients treated with liothyronine (L- T3) replacement therapy in preparation for diagnostic or therapeutic nuclear medicine procedures for the follow-up and management of differentiated thyroid cancer
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2020.
- Background: PubMed 11427693Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097.
- Background: PubMed 11844744Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev. 2002 Feb;23(1):38-89. doi: 10.1210/edrv.23.1.0455.
- Background: PubMed 8243325Nguyen TT, DiStefano JJ 3rd, Yamada H, Yen YM. Steady state organ distribution and metabolism of thyroxine and 3,5,3'-triiodothyronine in intestines, liver, kidneys, blood, and residual carcass of the rat in vivo. Endocrinology. 1993 Dec;133(6):2973-83. doi: 10.1210/endo.133.6.8243325.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kong Y Chen, Ph.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malignant Struma Ovarii and Papillary Thyroid Cancer, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. To assess the pharmacokinetics of T3 in patients devoid of endogenous or exogenous T4 during acute L-T3 withdrawal at steady- state and after the first L-T3 dose administration (time frame: 4 weeks after stopping L-T4 thyroid hormone replacement therapy and starting L-T3 treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01441154, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2020.