Thyroxine Titration Study
Recruitment status was Active, not recruiting
|First Received Date ICMJE||May 24, 2005|
|Last Updated Date||June 23, 2005|
|Start Date ICMJE||April 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Visual analog scales assessing wellbeing|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00111735 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Thyroxine Titration Study|
|Official Title ICMJE||What is the Optimal Serum TSH Concentration During Thyroxine Treatment for Primary Hypothyroidism? Effects of Fine Titration of Thyroxine Dosage on Wellbeing, Quality of Life and Cognitive Function|
The aim of the study is to examine the effects of fine titration of thyroxine dosage on symptoms of hypothyroidism, wellbeing and quality of life. The hypothesis is that symptoms of hypothyroidism, wellbeing and quality of life will be improved in thyroxine-treated subjects when serum thyrotropin (TSH) is suppressed and/or in the lower reference range, compared to when TSH is in the upper reference range.
Primary hypothyroidism is a common disorder, affecting 2% of the Australian population. The standard treatment is with thyroxine (T4), and conventionally, a serum thyrotropin (TSH) concentration within the laboratory range is taken as indicating adequacy of thyroxine dosage.
Some patients with hypothyroidism complain of persistently impaired well-being, despite taking thyroxine in a dose which normalises serum TSH concentrations. It is not clear whether this is because of comorbidity or because standard thyroxine replacement is in some way inadequate for some individuals.
The reference range for serum TSH is wide (currently 0.34-4.8 mU/L at PathCentre). The distribution of serum TSH concentrations in the population is skewed, with the mean and median in the lower reference range at approximately 1.0 mU/L. This has led some to argue that a serum TSH in the lower reference range should be the usual therapeutic target. Anecdotal evidence suggests that some thyroxine-treated patients do feel better if the thyroxine dose is adjusted so that serum TSH is in the lower reference range rather than the upper reference range. The National Academy for Clinical Biochemistry of the United States now recommends, that for thyroxine-treated patients, that serum TSH should be less than 2.0 mU/L. There is, however, no evidence from properly conducted studies that aiming for a serum TSH concentration in the lower reference range improves symptoms of hypothyroidism or general wellbeing, and this proposal has not been generally adopted.
Only one study examining the effects of fine titration of thyroxine dosage on wellbeing has been published. In this study, patients had significantly improved wellbeing if they took a dose of thyroxine which was 50 μg greater than their biochemically optimal dose as determined by a thyrotropin-releasing hormone test. In most cases, serum TSH was suppressed to below 0.2 mU/L (the limit of sensitivity of the assay) on the thyroxine doses which improved wellbeing. This study was open-label and non-randomised, and the results therefore may have been affected by bias.
A well-designed, double blind study of the effects of fine titration of thyroxine dosage on symptoms of hypothyroidism, wellbeing and quality of life is required to determine if a serum TSH in the lower reference range, rather than simply TSH within the reference range, should indeed be the usual therapeutic target for thyroxine therapy in primary hypothyroidism. It is also desirable to confirm the findings of Carr et al., that patients have improved wellbeing if TSH is suppressed to below normal levels.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Thyroxine|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Completion Date||March 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Australia|
|NCT Number ICMJE||NCT00111735|
|Other Study ID Numbers ICMJE||2003-015|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Sir Charles Gairdner Hospital|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||Sir Charles Gairdner Hospital|
|Verification Date||May 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP