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Trial registered on ANZCTR


Registration number
ACTRN12612000271808
Ethics application status
Approved
Date submitted
2/03/2012
Date registered
7/03/2012
Date last updated
7/03/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Hemostatic effects of levothyroxine and selenomethionine in euthyroid women with Hashimoto's thyroiditis
Scientific title
Hemostatic effects of levothyroxine and selenomethionine in euthyroid women with Hashimoto's thyroiditis: a six-month single-center, randomized, double-blind, placebo-controlled study
Secondary ID [1] 280064 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic lymphocytic thyroiditis, often referred to as Hashimoto's thyroiditis 285974 0
Condition category
Condition code
Metabolic and Endocrine 286162 286162 0 0
Thyroid disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The included Hashimoto’s thyroiditis patients were randomized in a double-blind manner to receive oral capsules of levothyroxine sodium (n=39) (arm 1), selenomethionine (n=39) (arm 2), levothyroxine sodium + selenomethionine (n=40) (arm 3), or of placebo (n=37) (arm 4) for six months. Levothyroxine was administered at the daily dose of 0.5 microg/kg for patients with TSH levels below 1.0 mIU/mL, 0.75 microg/kg for individuals with TSH levels between 1.0 and 2.0 mIU/mL, and 1 microg/kg for patients with a TSH above 2.0 mIU/mL. In turn, the dose of selenomethionine (200 microg daily) was independent of plasma TSH levels.
This study was in part a sub-study of another trial (ACTRN12611000238976), which assessed the effect of levothyroxine and selenomethionine, administered alone or in combination, on monocyte and lymphocyte cytokine release. The randomization procedure as well as treatment regimen in this study were the same as in ACTRN12611000238976 trial. Nineteen patients in arm 1, 20 patients in arm 2, 18 patients in arm 3, 16 patients in arm 4 and 18 healthy women simultaneously participated in in ACTRN12611000238976 trial, while the remaining ones only in this study. Because participation in both studies required collection of more blood sample volume, the participants were included in both studies only if they agreed on it. If not, they were included only in one of the two studies (using central randomization by computer).
The total duration of treatment: 6 months.
Intervention code [1] 284387 0
Treatment: Drugs
Comparator / control treatment
I – placebo (n=37) (oral microcellulose capsule taken once daily for 6 months) II – age-, weight-, blood pressure-, and lipid-profile-matched healthy women (n=39). They did not receive any specific intervention.
Control group
Placebo

Outcomes
Primary outcome [1] 286632 0
Plasma levels of fibrinogen (blood analysis)
Timepoint [1] 286632 0
Timepoint: at baseline and after three and six months of treatment
Primary outcome [2] 286654 0
Factor VII coagulant activity (blood analysis)
Timepoint [2] 286654 0
Timepoint: at baseline and after three and six months of treatment
Primary outcome [3] 286655 0
Plasma levels of plasminogen activator inhibitor-1 (blood analysis)
Timepoint [3] 286655 0
Timepoint: at baseline and after three and six months of treatment
Secondary outcome [1] 296331 0
The international normalized ratio (blood analysis)
Timepoint [1] 296331 0
Timepoint: at baseline and after three and six months of treatment
Secondary outcome [2] 296386 0
The activated partial prothrombin time (blood analysis)
Timepoint [2] 296386 0
Timepoint: at baseline and after three and six months of treatment
Secondary outcome [3] 296387 0
Plasma levels of von Willebrand factor (blood analysis)
Timepoint [3] 296387 0
Timepoint: at baseline and after three and six months of treatment
Secondary outcome [4] 296388 0
Plasma levels of factor X (blood analysis)
Timepoint [4] 296388 0
Timepoint: at baseline and after three and six months of treatment

Eligibility
Key inclusion criteria
(a) positive antibodies (>100 U/mL) against thyroid peroxidase (TPOAb), (b) the reduced echogenicity of the thyroid parenchyma on thyroid ultrasonography, (c) serum TSH less than 4.0 mU/L, and (d) plasma levels of free thyroxine (fT4) and free triiodothyronine (fT3)) within the reference range
Minimum age
18 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
A) any acute and chronic inflammatory processes
B) other autoimmune disorders
C) positive serum antibodies against TSH receptor
D) current treatment with thyroid hormones
E) concomitant treatment with drugs that may affect inflammatory processes in the vascular wall
F) concomitant treatment with other drugs known either to affect thyroid hormones or to interact with levothyroxine and selenomethionine
G) BMI>40 kg/m2
H) Turner or Down syndrome
I) any form of coronary artery disease
J) moderate or severe arterial hypertension (ESC/ESH grade 2 or 3)
K) symptomatic congestive heart failure
L) diabetes, impaired glucose tolerance or impaired fasting glucose
M) impaired renal or hepatic function
N) pregnancy or lactation
O) poor patient compliance

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomization by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
N/A
Phase
Phase 4
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/05/2005
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
155
Accrual to date
Final
Recruitment outside Australia
Country [1] 4181 0
Poland
State/province [1] 4181 0

Funding & Sponsors
Funding source category [1] 284814 0
Government body
Name [1] 284814 0
the Polish Committee of Scientific Research
Country [1] 284814 0
Poland
Primary sponsor type
Government body
Name
the Polish Committee of Scientific Research
Address
Wspolna 1/3 00-529, Warsaw
Country
Poland
Secondary sponsor category [1] 283695 0
None
Name [1] 283695 0
Address [1] 283695 0
Country [1] 283695 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
The aim of this study was to investigate the effects of levothyroxine and selenomethionine, administered alone or in combination, on hemostatic risk factors in Hashimoto’s thyroiditis patients with normal thyroid function tests. The study involved a group of 155 euthyroid women with recently diagnosed and previously untreated Hashimoto’s thyroiditis allocated into one of the following treatment options: levothyroxine, selenomethionine, levothyroxine and selenomethionine, or placebo. Levothyroxine was administered at the daily dose of 0.5 microg/kg for patients with TSH levels below 1.0 mIU/mL, 0.75 microg/kg for individuals with TSH levels between 1.0 and 2.0 mIU/mL, and 1 microg/kg for patients with a TSH above 2.0 mIU/mL. In turn, the dose of selenomethionine (200 microg daily) was independent of plasma TSH levels. Taking history, clinical examination and venous blood sampling for evaluating safety laboratory parameters were performed every 2 weeks. Compliance was assessed by pill counts during each visit and will be considered satisfactory when the number of tablets taken by a patient is ranged from 90% to 110% Laboratory assays were be performed three times: before treatment and after three and six months of levothyroxine and/or selenomethionine. We measured the international normalized ratio, the partial thromboplastin time, plasma levels/activities of fibrinogen, von Willebrand factor , factor VII, factor X and plasminogen activator inhibitor-1.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 33859 0
Address 33859 0
Country 33859 0
Phone 33859 0
Fax 33859 0
Email 33859 0
Contact person for public queries
Name 17106 0
Robert Krysiak (principal investigator), MD, PhD
Address 17106 0
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, PL 40-752 Katowice, Poland
Country 17106 0
Poland
Phone 17106 0
+48 32 2523902
Fax 17106 0
+48 32 2523902
Email 17106 0
[email protected]
Contact person for scientific queries
Name 8034 0
Robert Krysiak (principal investigator), MD, PhD
Address 8034 0
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, PL 40-752 Katowice, Poland
Country 8034 0
Poland
Phone 8034 0
+48 32 2523902
Fax 8034 0
+48 32 2523902
Email 8034 0
[email protected]

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