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
  Purpose

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.


Condition Intervention Phase
Secondary Hypothyroidism
Hypopituitarism
Hyperlipidemias
Drug: Thyroxin, Triiodothyronine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Controlled, Crossover Study: Treatment With Thyroxin Compared to Thyroxin + Triiodothyronin in Patients With Secondary Hypothyroidism

Resource links provided by NLM:


Further study details as provided by University Hospital Freiburg:

Primary Outcome Measures:
  • well-being [ Time Frame: 3 weeks of treatment ]
  • cognitive function [ Time Frame: 3 weeks of treatment ]

Secondary Outcome Measures:
  • lipid metabolism [ Time Frame: 3 weeks of treatment ]
  • muscle function / ankle reflex time [ Time Frame: 3 weeks of treatment ]

Estimated Enrollment: 25
Study Start Date: February 2004
Study Completion Date: April 2007
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00360074

Locations
Germany
University Hospital Freiburg, Department of Medicine
Freiburg, Baden-Württemberg, Germany, 79104
Sponsors and Collaborators
University Hospital Freiburg
Investigators
Principal Investigator: Prof Dr Martin Reincke, MD former Medical Professor of University Hospital Freiburg
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00360074     History of Changes
Other Study ID Numbers: FH 326/03
Study First Received: August 2, 2006
Last Updated: June 6, 2008
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Freiburg:
secondary hypothyroidism
body weight adjusted thyroxin dose
triiodothyronine supplementation

Additional relevant MeSH terms:
Hypopituitarism
Neoplasm Metastasis
Hyperlipidemias
Hypothyroidism
Neoplastic Processes
Neoplasms
Pathologic Processes
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Thyroid Diseases
Endocrine System Diseases
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on September 22, 2014