The Effect of Thyroid Hormone on Drug Elimination in Cancer Patients
Tracking Information | |
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First Received Date ICMJE | April 7, 2004 |
Last Updated Date | March 3, 2008 |
Start Date ICMJE | April 2004 |
Primary Completion Date | |
Current Primary Outcome Measures ICMJE | |
Original Primary Outcome Measures ICMJE | |
Change History | Complete list of historical versions of study NCT00080574 on ClinicalTrials.gov Archive Site |
Current Secondary Outcome Measures ICMJE | |
Original Secondary Outcome Measures ICMJE | |
Current Other Outcome Measures ICMJE | |
Original Other Outcome Measures ICMJE | |
Descriptive Information | |
Brief Title ICMJE | The Effect of Thyroid Hormone on Drug Elimination in Cancer Patients |
Official Title ICMJE | The Effects of Thyroid Hormone on Cytochrome P450 and P-Glycoprotein Activity in Thyroid Cancer Patients |
Brief Summary | This study will examine whether and how levothyroxine (Synthroid, a synthetic thyroid hormone) affects the way the body handles other drugs. If levothyroxine does affect the metabolism of other drugs, the dose of those medications may need to be increased to enhance their action or decreased to avoid adverse reactions. Patients 18 years of age and older with thyroid cancer who are participating in NIH protocol #77-DK-0096 and are receiving long-term suppression therapy with levothyroxine may be eligible for this study. This is not a study of thyroid cancer or of potential new drugs to treat it. Thyroid cancer patients are being studied because their treatment regimen provides an opportunity to study drug metabolism while patients are both on and off levothyroxine therapy. Participants come to the NIH Clinical Center on two occasions: once while they are regularly taking their levothyroxine, and once while they are off the medication in preparation for their radioactive iodide diagnostic scan for the procedures outlined below. The time interval between the two clinic visits depends on whether the first visit is while the patient is on or off medication. Participants are asked to fast overnight before each visit and to abstain from certain foods and beverages for 48 to 72 hours before the visit. At each visit, patients undergo the following procedures:
Participants may resume their normal diet 4 hours after taking the study medications. |
Detailed Description | Interaction between thyroid hormones and commonly prescribed drugs has been well documented, resulting in augmentation or attenuation of the action of either compound. Phase I drug metabolism is mediated mostly by enzymes belonging to the cytochrome p450 superfamily. Studies in animals and cell cultures have shown that thyroid hormones play an important role in the constitutive expression of the p450 enzymes, thus potentially altering the metabolism and the effects of a variety of drugs. P-glycoprotein is expressed in the major organs associated with drug absorption, distribution, and elimination from the body (e.g. intestine, kidney, liver, skin, and the blood-brain barrier). Expression of intestinal P-glycoprotein in humans also appears to be influenced by thyroid hormones. We intend to study the effect of thyroid hormones on the activity of CYP1A2, CYP2C19, CYP2D6, CYP3A4 and P-glycoprotein by using a five-drug cocktail (caffeine, omeprazole, dextromethorphan, midazolam, and fexofenadine) administered in patients with thyroid cancer, both on thyroid hormone suppression therapy (in conditions of subclinical hyperthyroidism) and off this treatment (in conditions of hypothyroidism) at the time of their routine radioactive iodine scan. Additionally we will perform two skin biopsies in order to assess the pattern of expression of metabolic enzymes and drug transport proteins on and off thyroid hormone suppression therapy. |
Study Type ICMJE | Interventional |
Study Phase | Phase 2 |
Study Design ICMJE | Endpoint Classification: Safety/Efficacy Study Primary Purpose: Treatment |
Condition ICMJE | Thyroid Cancer |
Intervention ICMJE | Procedure: Skin Biopsy |
Study Arm (s) | |
Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |
Recruitment Status ICMJE | Completed |
Enrollment ICMJE | 20 |
Completion Date | November 2005 |
Primary Completion Date | |
Eligibility Criteria ICMJE | INCLUSION CRITERIA:
EXCLUSION CRITERIA: Subject is pregnant, currently breast-feeding, practicing birth control with hormonal contraceptives, or is on hormone replacement therapy (HRT). Subject is a smoker. Subject has a confounding medical illness (es) that in the judgement of the investigators would pose an added risk for the subject (e.g. severe respiratory disease). Subject has a history of substance abuse within the past 5 years or drug or alcohol use, that may affect enzyme levels and function. Caffeine or caffeine-containing beverages and chocolate bars consumption within 48 hours of scheduled caffeine administration for CYP1A2 phenotyping; scheduled omeprazole administration during or within 14 days of the study; scheduled dextromethorphan administration during or within 30 days of study; scheduled fexofenadine administration during or within 7 days of the study. AST or ALT greater than or equal to 2 times the upper normal reference limit. Concurrent administration of known CYP and/or P-gp inducers (barbiturates, phenytoin, carbamazepine, rifampicin) and inhibitors (amiodarone, atorvastatin, chloroquine, cimetidine, co-trimoxazole, cyclosporine, diltazem, erythromycin, fluoxetine fluvoxamine, isoniazid, itrakonazole, ketokonazole, metronidazole, mexiletine, nefazadone, norfloxacin, verapamil) or use of any alternative/complementary therapies for at least 30 days prior to study or during the study. Non-herbal vitamin and mineral preparations will be allowed. Inability to obtain venous access for sample collection, or basal hemoglobin of equal or less than 10 g/dl. Patients receiving scheduled therapy with alprazolam, triazolam, clonazepam, diazepam, lorazepam, oxazepam, temazepam or chlorodiazepoxide, during or within 30 days of study. Patients consuming grapefruit products (juice or the fresh fruit), apple and orange juice during or within 72 hrs of study. History of intolerance to caffiene, omeprazole, dextromethorphan, midazolam or fexofenadine. The presence of persistent diarrhea or malabsorption syndromes that would interfere with the patient's ability to adequately absorb drugs; and/or Patients receiving monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, and isocarboxazid. Patients with a history of cheloids formation. |
Gender | Both |
Ages | |
Accepts Healthy Volunteers | No |
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects |
Location Countries ICMJE | United States |
Administrative Information | |
NCT Number ICMJE | NCT00080574 |
Other Study ID Numbers ICMJE | 040140, 04-DK-0140 |
Has Data Monitoring Committee | |
Responsible Party | |
Study Sponsor ICMJE | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
Collaborators ICMJE | |
Investigators ICMJE | |
Information Provided By | National Institutes of Health Clinical Center (CC) |
Verification Date | November 2005 |
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |