Secondary HypothyroidismPhase 4NCT00360074
Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
A Phase 4 study testing Thyroxin, Triiodothyronine in people with Secondary Hypothyroidism and Hypopituitarism, run by University Hospital Freiburg at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Secondary Hypothyroidism, Hypopituitarism, Hyperlipidemias
- What is being tested?
- Thyroxin, Triiodothyronine
- How many people
- 25 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2004to Apr 2007
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- history of cardiovascular or pulmonary diseases
- current thyroxin dosage > 1.6 µg/kg bw
- pregnancy
- epilepsy
- cerebrovascular diseases
- nodular goiter
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Freiburg, Department of Medicine
Freiburg im Breisgau, Baden-Wurttemberg, 79104
About this study
Official title: 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.
Read the 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.
- Conditions
- Secondary Hypothyroidism, Hypopituitarism, Hyperlipidemias
- Being tested
- Thyroxin, Triiodothyronine
- Keywords
- secondary hypothyroidism, body weight adjusted thyroxin dose, triiodothyronine supplementation
- Medical subject headings
- Hypothyroidism, Hypopituitarism, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thyroxin, TriiodothyronineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
well-being
Measured: 3 weeks of treatment
cognitive function
Measured: 3 weeks of treatment
Secondary outcomes (2)
lipid metabolism
Measured: 3 weeks of treatment
muscle function / ankle reflex time
Measured: 3 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2006 (estimated)
- Study startFeb 2004
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Secondary HypothyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 25 participants
Sponsor and investigators
- Lead sponsor
- University Hospital Freiburg
- Sponsor type
- University, hospital or other
- Investigators
- Prof Dr Martin Reincke, MD, Principal investigator, former Medical Professor of University Hospital Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00360074
- Sponsor's protocol ID
- FH 326/03
- Status last verified
- Jun 2008
- First submitted
- 2 Aug 2006
- Last updated
- 9 Jun 2008
- Results posted
- No
Publications
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. doi: 10.1210/jc.2007-0297. Epub 2007 Aug 21.
PubMed 17711927
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Controlled, Crossover Study: Treatment With Thyroxin Compared to Thyroxin + Triiodothyronin in Patients With Secondary Hypothyroidism
- ClinicalTrials.gov ID
- NCT00360074
- Acronym / sponsor ID
- FH 326/03
- Conditions
- Secondary Hypothyroidism, Hypopituitarism, Hyperlipidemias
- Keywords
- secondary hypothyroidism, body weight adjusted thyroxin dose, triiodothyronine supplementation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants
- Lead sponsor
- University Hospital FreiburgUniversity, hospital or other
- Study start
- Feb 2004
- Study completion
- Apr 2007 (actual)
- First posted
- 3 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- history of cardiovascular or pulmonary diseases
- current thyroxin dosage > 1.6 µg/kg bw
- pregnancy
- epilepsy
- cerebrovascular diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thyroxin, Triiodothyronine | Drug | – |
Primary outcome
well-being
Time frame: 3 weeks of treatment
cognitive function
Time frame: 3 weeks of treatment
2 secondary outcomes
lipid metabolism
Time frame: 3 weeks of treatment
muscle function / ankle reflex time
Time frame: 3 weeks of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2008.
- Results publication: PubMed 17711927Slawik 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. doi: 10.1210/jc.2007-0297. Epub 2007 Aug 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof Dr Martin Reincke, MD principal investigator
former Medical Professor of University Hospital Freiburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Thyroxin, Triiodothyronine in people with Secondary Hypothyroidism and Hypopituitarism, run by University Hospital Freiburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
well-being (time frame: 3 weeks of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00360074, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2008.