Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00080574
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2004-04-07
Brief Title:
The Effect of Thyroid Hormone on Drug Elimination in Cancer Patients
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
The Effects of Thyroid Hormone on Cytochrome P450 and P-Glycoprotein Activity in Thyroid Cancer Patients
Status:
COMPLETED
Status Verified Date:
2005-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
Medication history limited physical examination and blood draw for laboratory tests including a test to look for genes important in eliminating medications from the body
Insertion of a catheter thin plastic tube into an arm vein for collecting blood samples
Shave skin biopsy optional to explore how proteins in the skin that metabolize and transport drugs are affected by thyroid hormone For this procedure the skin is cleaned numbed with medicine and a small sample of the top layer is removed with a razor blade The wound heals in 2 to 3 days
Medication dosing Participants take all of the following substances by mouth at the same time 1 200 mg of caffeine a compound commonly found in chocolate sodapop coffee tea and non-prescription products to prevent sleep 2 30 mg of dextromethorphan a non-prescription cough suppressant 3 40 mg of omeprazole a prescription drug for heartburn and stomach ulcers 4 8 mg of midazolam a prescription drug used to cause relaxation and drowsiness and 5 120 mg of fexofenadine a non-sedating prescription antihistamine used to treat allergies
Blood and urine sampling Fifteen blood samples of about 5 mL 1 teaspoon each are collected through the catheter and urine is collected over the next 24 hours to determine what happens to the test drugs in the body
Participants may resume their normal diet 4 hours after taking the study medications
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
Medication history limited physical examination and blood draw for laboratory tests including a test to look for genes important in eliminating medications from the body
Insertion of a catheter thin plastic tube into an arm vein for collecting blood samples
Shave skin biopsy optional to explore how proteins in the skin that metabolize and transport drugs are affected by thyroid hormone For this procedure the skin is cleaned numbed with medicine and a small sample of the top layer is removed with a razor blade The wound heals in 2 to 3 days
Medication dosing Participants take all of the following substances by mouth at the same time 1 200 mg of caffeine a compound commonly found in chocolate sodapop coffee tea and non-prescription products to prevent sleep 2 30 mg of dextromethorphan a non-prescription cough suppressant 3 40 mg of omeprazole a prescription drug for heartburn and stomach ulcers 4 8 mg of midazolam a prescription drug used to cause relaxation and drowsiness and 5 120 mg of fexofenadine a non-sedating prescription antihistamine used to treat allergies
Blood and urine sampling Fifteen blood samples of about 5 mL 1 teaspoon each are collected through the catheter and urine is collected over the next 24 hours to determine what happens to the test drugs in the body
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 eg 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-DK-0140 | None | None | None |