Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation

This study has been completed.
Sponsor:
Information provided by:
University Hospital Freiburg
ClinicalTrials.gov Identifier:
NCT00360074
First received: August 2, 2006
Last updated: June 6, 2008
Last verified: June 2008

August 2, 2006
June 6, 2008
February 2004
Not Provided
  • well-being [ Time Frame: 3 weeks of treatment ]
  • cognitive function [ Time Frame: 3 weeks of treatment ]
  • well-being
  • cognitive function
Complete list of historical versions of study NCT00360074 on ClinicalTrials.gov Archive Site
  • lipid metabolism [ Time Frame: 3 weeks of treatment ]
  • muscle function / ankle reflex time [ Time Frame: 3 weeks of treatment ]
  • lipid metabolism
  • muscle function / ankle reflex time
Not Provided
Not Provided
 
Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
A Randomised, Controlled, Crossover Study: Treatment With Thyroxin Compared to Thyroxin + Triiodothyronin in Patients With Secondary Hypothyroidism

The purpose of this study is to determine whether a body weight adjusted dose of thyroxin is superior to treatment guided by laboratory results of thyroxin hormones in patients with central hypothyroidism. Moreover beneficial effects of triiodthyronine supplementation are investigated.

Backround: A normal thyroid function is critical for metabolism, well-being and cognitive function. It is now well accepted that primary subclinical hypothyroidism, characterized by normal circulating thyroid hormones (fT3 and fT4) and elevated TSH, should be treated to improve reduced quality of life and abnormalities of lipid metabolism. In central hypothyroidism (CH) the dose of replacement therapy aims to achieve normal thyroxin (T4) concentrations as defined by appropriate reference populations. Adequate thyroxin treatment is especially challenging, as T4 cannot be titrated according to endogenous TSH levels because of the impaired hypothalamic-pituitary unit. The majority of untreated CH patients show normal (40 %) or elevated TSH levels (35 %) while only a minority has reduced concentrations (25 %) {Faglia, 1979 #1}. These findings are explained by the lack of pulsatile secretion and nocturnal TSH surge, which has been attributed to impaired thyrotroph function in CH patients {Caron, 1986 #2}. Moreover, impaired biological activity of TSH itself due to reduced glycosylation has been described in secondary hypothyroidism.

In a cross sectional study performed in patients with central hypothyroidism, we found elevated cholesterol levels and increased ankle reflex time suggesting subtle hypothyroidism, though fT3 and fT4 serum concentrations were within the normal range. The average dose of thyroxin (T4) applied in these patients with central hypothyroidism was 1.1 µg/kg bw, which is below the average dose recommended in primary hypothyroidism (1.6 µg/kg bw). We hypothesized that these results might indicate suboptimal T4 replacement therapy, not detectable by current laboratory testing.

Hypothesis: To investigate the effects of a body weight adjusted T4 or T3T4 dose on metabolism, well-being and cognitive function.

Study design: Placebo controlled trial in patients with central hypothyroidism following a double blind cross-over design.

Intervention: Three different treatment regimes (5 weeks each) were compared: "CON-T4", empirically chosen, current dose of T4 (1 ± 0.05 μg/kg body weight (bw); "OPT-T4", optimized T4 treatment (1.6 μg/kg bw T4); "T3T4", combination of triiodothyronine (T3, 0.16) and T4 (1.44 μg/kg bw). Biochemical parameters, ankle reflex time and neurocognitive functions were assessed.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Secondary Hypothyroidism
  • Hypopituitarism
  • Hyperlipidemias
Drug: Thyroxin, Triiodothyronine
Not Provided
Slawik M, Klawitter B, Meiser E, Schories M, Zwermann O, Borm K, Peper M, Lubrich B, Hug MJ, Nauck M, Olschewski M, Beuschlein F, Reincke M. Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine. J Clin Endocrinol Metab. 2007 Nov;92(11):4115-22. Epub 2007 Aug 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
April 2007
Not Provided

Inclusion Criteria:

  • hypopituitarism of at least 3 axes (TSH plus gonadotropin, somatotropin, corticotropin or ADH deficiency)
  • termination of surgical or radiation treatment of pituitary tumors at least six month before study entry
  • BMI of 20 - 39.9 kg/m2
  • non-smoking status.

Exclusion Criteria:

  • history of cardiovascular or pulmonary diseases
  • current thyroxin dosage > 1.6 µg/kg bw
  • pregnancy
  • epilepsy
  • cerebrovascular diseases
  • nodular goiter
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00360074
FH 326/03
Not Provided
Not Provided
University Hospital Freiburg
Not Provided
Principal Investigator: Prof Dr Martin Reincke, MD former Medical Professor of University Hospital Freiburg
University Hospital Freiburg
June 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP