HypothyroidismNCT01801033
Effects of Thyroid Hormone Enzyme Blocking on Hypothyroidism
An observational study of Hypothyroidism and Thyroidectomy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Trial summary
Background: Hypothyroidism is a condition caused by the loss of function of the thyroid gland. The thyroid gland produces two hormones, T4 and T3. These hormones control the metabolism and function of many organs. Lack of energy, depression, and constipation are common symptoms of hypothyroidism. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypothyroidism, Thyroidectomy
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 4 Jan 2013to 29 Nov 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- <TAB>Thyroid uptake > 5% at 24 hours on (123)I thyroid scan while on replacement therapy (in patients with thyroid gland residue > 2 mL by ultrasound).
- <TAB>Patients who have lipid disorders requiring pharmacologic intervention.
- <TAB>Any elevation of AST or ALT above upper limit of normal range.
- <TAB>Any reduction of the WBC count below the lower limit of normal range.
- <TAB>History of, and/or current diabetes mellitus (fasting glucose >126 mg/dL or current pharmacologic treatment).
- <TAB>Hypertension requiring pharmacologic intervention.
Show all 14Show fewer
- <TAB>Female patients who are on hormonal contraceptives or are breastfeeding.
- <TAB>Use of beta blocker medications and amiodarone.
- <TAB>Pregnancy (women of child-bearing age must have a negative pregnancy test prior to inclusion).
- <TAB>History of vasculitis, viral hepatitis (except A), granulocytopenia.
- <TAB>Known allergy or serious adverse event to PTU.
- <TAB>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 PTU. Should study volunteers receive other pharmacologic interventions a clinical pharmacist will be consulted to evaluate potential drug-drug interactions.
- <TAB>Presence of persistent diarrhea or malabsorption syndromes that would interfere with the patient s ability to adequately absorb medications.
- <TAB>Inability to obtain venous access for sample collection, or basal hemoglobin of less than or equal to 12 g/dl.
About this study
Official title: Effects of Pharmacologic Block of Type-1 Deiodinase on Thyroid Hormone Action and on the Circulating Levels of T3 in Hypothyroid Patients
Background:
- Hypothyroidism is a condition caused by the loss of function of the thyroid gland. The thyroid gland produces two hormones, T4 and T3. These hormones control the metabolism and function of many organs. Lack of energy, depression, and constipation are common symptoms of hypothyroidism. T4 is converted into T3, the active form of thyroid hormone, by two enzymes called deiodinases. People with hypothyroidism are treated with a synthetic T4 hormone, which the enzymes convert to T3. This treatment is usually effective, but some people continue to have symptoms even after treatment. Some researchers think that this may be caused by a problem with the enzymes that convert T4 into T3. They want to look at how the enzymes regulate the levels of T4 and T3 in the blood. They will do so by using a drug that blocks the action of one of the two enzymes.
Read more
Objectives:
- To look at how thyroid hormone enzyme blocking affects hypothyroidism treatment medication.
Eligibility:
- Individuals at least 18 years of age who have hypothyroidism and are on thyroid hormone replacement therapy.
Design:
- The study consists of one screening visit, 9 days of inpatient hospital admission, and a follow-up visit 2 weeks after discharge.
- Participants will be screened with a physical exam and medical history. They will provide blood samples.
- Participants will receive balanced-diet meals to take home for the 2 days before they enter the hospital. They will continue this diet while in the hospital.
- During the inpatient stay, participants will be monitored with regular blood tests. They will have the following procedures:
- Continued thyroid hormone replacement for all 9 days.
- Drug to block thyroid enzyme for 7 days.
- Metabolism test, with room temperature changes, on days 1, 2, 5, 8, and 9.
- Measurements of body fat on days 2, 5, and 8.
- Blood glucose tests on days 1 and 9.
- Muscle contraction tests on days 1, 2, 4, 5, 8, and 9.
- Heart imaging studies on days 2, 5, and 8.
- Optional skeletal muscle and fat tissue biopsies on days 1 and 9.
- There will be a follow-up visit 2 weeks after leaving the hospital. Participants will have a final physical exam and provide blood samples.
Read the detailed description
Thyroid hormone action is an important regulator of the metabolism and the function of many organs. The active form of thyroid hormone is T3, and its blood and tissue levels are the result of the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, of the peripheral conversion of T4 into T3, and of the degradation of these hormones. In hypothyroid patients (particularly patients who underwent total thyroidectomy), the levels of T3 are entirely dependent on the exogenously administered T4 (Levothyroxine, L-T4) which is converted to T3 or to the inactive form, rT3, by enzymes called deiodinases. This complex system has only been partially studied in humans and very little is known about the correlation between circulating levels of T3 and end-organ target tissue thyroid hormone action.
The aim of this protocol is to characterize the contribution of the two activating deiodinases (type-1 and type-2) to the blood levels and biological effects of T3. To achieve this goal we intend to study hypothyroid patients treated with adequate replacement of L-T4 therapy while simultaneously blocking the activity of the type-1 deiodinase with propylthiouracil (PTU).
Twenty hypothyroid patients who underwent total thyroidectomy or are affected by hypothyroidism and are on L-T4 therapy with normal TSH values will be recruited. After enrollment in the study, the patients eligibility will be determined during an outpatient visit. Patients will be admitted to the NIH Clinical Center for a 9-day period and will receive PTU at a dose of 200 mg four times daily for seven days. During the hospitalization for this research protocol, the following studies will be performed: serial blood sampling for circulating thyroid hormones to obtain pharmacokinetic parameters of T3, lipids, glucose and insulin; body composition; resting energy expenditure at room temperature and during exposure to mild cold; echocardiogram and EKG; skeletal muscle strength measurement and cardiac MRI.
The results obtained from this study will help in further characterizing the effects of thyroid hormone on metabolism, and may lead to important information on how to optimize the thyroid hormone replacement therapy for the treatment of hypothyroidism.
- Conditions
- Hypothyroidism, Thyroidectomy
- Keywords
- Trioodothyronine (T3), Thyroid Hormone Action, Deiodinases, Hypothyroid, Propylthiouracil (PTU)
- Medical subject headings
- Hypothyroidism
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the changes in glucose metabolism (hepatic gluconeogenesis and insulin-mediated glucose disposal).
Measured: 9 days
To serially evaluate the changes in end-organ effects of thyroid hormones during pharmacologic block of D1, specifically: 1. To assess the changes in lipid metabolism parameters (total cholesterol, LDL cholesterol, apolipoproteins).
Measured: 9 days
To assess the changes in resting energy expenditure.
Measured: 9 days
To assess the changes in facultative thermogenesis as measured in respiration chamber (at 19 (Infinite)C and 24 (Infinite)C).
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2013 (estimated)
- Study start4 Jan 2013
- Primary completion29 Nov 2013
- Study completion29 Nov 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 HypothyroidismStudies 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
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Francesco S Celi, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01801033
- Sponsor's protocol ID
- 130058
- Other IDs
- 13-DK-0058
- Status last verified
- 29 Nov 2013
- First submitted
- 26 Feb 2013
- Last updated
- 6 Oct 2017
- Results posted
- No
Publications
Mentuccia D, Proietti-Pannunzi L, Tanner K, Bacci V, Pollin TI, Poehlman ET, Shuldiner AR, Celi FS. Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes. 2002 Mar;51(3):880-3. doi: 10.2337/diabetes.51.3.880.
PubMed 11872697Mandel SJ, Berry MJ, Kieffer JD, Harney JW, Warne RL, Larsen PR. Cloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase. J Clin Endocrinol Metab. 1992 Oct;75(4):1133-9. doi: 10.1210/jcem.75.4.1400883.
PubMed 1400883Peeters RP, van Toor H, Klootwijk W, de Rijke YB, Kuiper GG, Uitterlinden AG, Visser TJ. Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab. 2003 Jun;88(6):2880-8. doi: 10.1210/jc.2002-021592.
PubMed 12788902
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Pharmacologic Block of Type-1 Deiodinase on Thyroid Hormone Action and on the Circulating Levels of T3 in Hypothyroid Patients
- ClinicalTrials.gov ID
- NCT01801033
- Acronym / sponsor ID
- 130058
- Conditions
- Hypothyroidism, Thyroidectomy
- Keywords
- Trioodothyronine (T3), Thyroid Hormone Action, Deiodinases, Hypothyroid, Propylthiouracil (PTU)
- Study type
- Observational
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 4 Jan 2013
- Primary completion
- 29 Nov 2013 (actual)
- Study completion
- 29 Nov 2013 (actual)
- First posted
- 28 Feb 2013 (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:
- Hypothyroidism is a condition caused by the loss of function of the thyroid gland. The thyroid gland produces two hormones, T4 and T3. These hormones control the metabolism and function of many organs. Lack of energy, depression, and constipation are common symptoms of hypothyroidism. T4 is converted into T3, the active form of thyroid hormone, by two enzymes called deiodinases. People with hypothyroidism are treated with a synthetic T4 hormone, which the enzymes convert to T3. This treatment is usually effective, but some people continue to have symptoms even after treatment. Some researchers think that this may be caused by a problem with the enzymes that convert T4 into T3. They want to look at how the enzymes regulate the levels of T4 and T3 in the blood. They will do so by using a drug that blocks the action of one of the two enzymes.
Objectives:
- To look at how thyroid hormone enzyme blocking affects hypothyroidism treatment medication.
Eligibility:
- Individuals at least 18 years of age who have hypothyroidism and are on thyroid hormone replacement therapy.
Design:
- The study consists of one screening visit, 9 days of inpatient hospital admission, and a follow-up visit 2 weeks after discharge.
- Participants will be screened with a physical exam and medical history. They will provide blood samples.
- Participants will receive balanced-diet meals to take home for the 2 days before they enter the hospital. They will continue this diet while in the hospital.
- During the inpatient stay, participants will be monitored with regular blood tests. They will have the following procedures:
- Continued thyroid hormone replacement for all 9 days.
- Drug to block thyroid enzyme for 7 days.
- Metabolism test, with room temperature changes, on days 1, 2, 5, 8, and 9.
- Measurements of body fat on days 2, 5, and 8.
- Blood glucose tests on days 1 and 9.
- Muscle contraction tests on days 1, 2, 4, 5, 8, and 9.
- Heart imaging studies on days 2, 5, and 8.
- Optional skeletal muscle and fat tissue biopsies on days 1 and 9.
- There will be a follow-up visit 2 weeks after leaving the hospital. Participants will have a final physical exam and provide blood samples.
Detailed description
Thyroid hormone action is an important regulator of the metabolism and the function of many organs. The active form of thyroid hormone is T3, and its blood and tissue levels are the result of the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, of the peripheral conversion of T4 into T3, and of the degradation of these hormones. In hypothyroid patients (particularly patients who underwent total thyroidectomy), the levels of T3 are entirely dependent on the exogenously administered T4 (Levothyroxine, L-T4) which is converted to T3 or to the inactive form, rT3, by enzymes called deiodinases. This complex system has only been partially studied in humans and very little is known about the correlation between circulating levels of T3 and end-organ target tissue thyroid hormone action.
The aim of this protocol is to characterize the contribution of the two activating deiodinases (type-1 and type-2) to the blood levels and biological effects of T3. To achieve this goal we intend to study hypothyroid patients treated with adequate replacement of L-T4 therapy while simultaneously blocking the activity of the type-1 deiodinase with propylthiouracil (PTU).
Twenty hypothyroid patients who underwent total thyroidectomy or are affected by hypothyroidism and are on L-T4 therapy with normal TSH values will be recruited. After enrollment in the study, the patients eligibility will be determined during an outpatient visit. Patients will be admitted to the NIH Clinical Center for a 9-day period and will receive PTU at a dose of 200 mg four times daily for seven days. During the hospitalization for this research protocol, the following studies will be performed: serial blood sampling for circulating thyroid hormones to obtain pharmacokinetic parameters of T3, lipids, glucose and insulin; body composition; resting energy expenditure at room temperature and during exposure to mild cold; echocardiogram and EKG; skeletal muscle strength measurement and cardiac MRI.
The results obtained from this study will help in further characterizing the effects of thyroid hormone on metabolism, and may lead to important information on how to optimize the thyroid hormone replacement therapy for the treatment of hypothyroidism.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- <TAB>Thyroid uptake > 5% at 24 hours on (123)I thyroid scan while on replacement therapy (in patients with thyroid gland residue > 2 mL by ultrasound).
- <TAB>Patients who have lipid disorders requiring pharmacologic intervention.
- <TAB>Any elevation of AST or ALT above upper limit of normal range.
- <TAB>Any reduction of the WBC count below the lower limit of normal range.
- <TAB>History of, and/or current diabetes mellitus (fasting glucose >126 mg/dL or current pharmacologic treatment).
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
To assess the changes in glucose metabolism (hepatic gluconeogenesis and insulin-mediated glucose disposal).
Time frame: 9 days
To serially evaluate the changes in end-organ effects of thyroid hormones during pharmacologic block of D1, specifically: 1. To assess the changes in lipid metabolism parameters (total cholesterol, LDL cholesterol, apolipoproteins).
Time frame: 9 days
To assess the changes in resting energy expenditure.
Time frame: 9 days
To assess the changes in facultative thermogenesis as measured in respiration chamber (at 19 (Infinite)C and 24 (Infinite)C).
Time frame: 9 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2017.
- Background: PubMed 11872697Mentuccia D, Proietti-Pannunzi L, Tanner K, Bacci V, Pollin TI, Poehlman ET, Shuldiner AR, Celi FS. Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes. 2002 Mar;51(3):880-3. doi: 10.2337/diabetes.51.3.880.
- Background: PubMed 1400883Mandel SJ, Berry MJ, Kieffer JD, Harney JW, Warne RL, Larsen PR. Cloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase. J Clin Endocrinol Metab. 1992 Oct;75(4):1133-9. doi: 10.1210/jcem.75.4.1400883.
- Background: PubMed 12788902Peeters RP, van Toor H, Klootwijk W, de Rijke YB, Kuiper GG, Uitterlinden AG, Visser TJ. Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab. 2003 Jun;88(6):2880-8. doi: 10.1210/jc.2002-021592.
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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.
Francesco S Celi, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Questions about this trial
What is this clinical trial studying?
An observational study of Hypothyroidism and Thyroidectomy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
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 0 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: withdrawn, as of the sponsor's last update on 6 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
To assess the changes in glucose metabolism (hepatic gluconeogenesis and insulin-mediated glucose disposal). (time frame: 9 days). The study lists 4 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 NCT01801033, 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 6 Oct 2017.