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Trial registered on ANZCTR


Registration number
ACTRN12611000238976
Ethics application status
Approved
Date submitted
1/03/2011
Date registered
4/03/2011
Date last updated
4/03/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto’s thyroiditis
Scientific title
The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto’s thyroiditis: a six-month single-center, randomized, double-blind, placebo-controlled study
Secondary ID [1] 259697 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 261271 0
Condition category
Condition code
Metabolic and Endocrine 259423 259423 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=42) (arm 1), selenomethionine (n=43) (arm 2), levothyroxine sodium + selenomethionine (n=43) (arm 3), or of placebo (n=42) (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.
The total duration of treatment: 6 months, the total duration of follow-up: 12 months
Intervention code [1] 264126 0
Treatment: Drugs
Comparator / control treatment
I – placebo (oral microcellulose capsule taken once daily for 6 months) (n=42)
II – age-, weight-, blood pressure-, and lipid-profile-matched healthy women (n=41). They did not receive any specific intervention.
Control group
Placebo

Outcomes
Primary outcome [1] 262230 0
Primary Outcome 1: Monocyte release of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1 (cell cultures, assays in supernatants, ELISA method)
Timepoint [1] 262230 0
Timepoint: at baseline and after three and six months of treatment
Primary outcome [2] 262231 0
Primary Outcome 2: Lymphocyte release of tumor necrosis factor-alpha, interleukin-2, interferon-gamma (cell cultures, assays in supernatants, ELISA method)
Timepoint [2] 262231 0
Timepoint: at baseline and after three and six months of treatment
Primary outcome [3] 262232 0
Primary Outcome 3: Plasma levels of high sensitivity C-reactive protein (cell cultures, assays in supernatants, ELISA method)
Timepoint [3] 262232 0
Timepoint: at baseline and after three and six months of treatment
Secondary outcome [1] 273361 0
Monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of hsCRP between smokers and non-smokers (cell cultures, assays in supernatants, ELISA method)
Timepoint [1] 273361 0
Timepoint: at baseline and after three and six months of treatment

Eligibility
Key inclusion criteria
Hashimoto's thyroiditis patients:
A) females between the ages of 18 and 60 years
B) positive antibodies (>100 U/mL) against thyroid peroxidase
C) the reduced echogenicity of the thyroid parenchyma on thyroid ultrasonography
D) euthyroid function (TSH < 4.0 mU/L, normal values for free thyroxine and free triiodothyronine)

Control Group II:
age-, weight-, blood pressure-, and lipid-profile-matched healthy women

Participants were medically stable, and, in the judgment of the investigators, otherwise acceptable for entry on the basis of the findings of medical history, physical examination, and routine laboratory tests
Minimum age
18 Years
Maximum age
60 Years
Gender
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
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 3244 0
Poland
State/province [1] 3244 0

Funding & Sponsors
Funding source category [1] 264580 0
Government body
Name [1] 264580 0
the Polish Committee of Scientific Research
Address [1] 264580 0
Wspolna 1/3 00-529, Warsaw
Country [1] 264580 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] 263720 0
None
Name [1] 263720 0
Address [1] 263720 0
Country [1] 263720 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260570 0
Bioethics Committee of the Medical University of Silesia
Ethics committee address [1] 260570 0
Poniatowskiego 15, 40-055 Katowice
Ethics committee country [1] 260570 0
Poland
Date submitted for ethics approval [1] 260570 0
01/03/2005
Approval date [1] 260570 0
15/03/2005
Ethics approval number [1] 260570 0
KNW/0022/KB1/91/05

Summary
Brief summary
The aim of the study was to compare the effect of levothyroxine and selenomethionine on monocyte and lymphocyte cytokine release and systemic inflammation in patients with Hashimoto’s thyroiditis. The study was a six-month single-center, randomized, double-blind, placebo-controlled study. The included patients with Hashimoto’s thyroiditis were randomized in a double-blind manner to receive levothyroxine sodium (n=42), selenomethionine (n=43), levothyroxine sodium + selenomethionine (n=43), or placebo (n=42). Levothyroxine was administered at the daily dose of 0.5 µg/kg for patients with TSH levels below 1.0 mIU/mL, 0.75 µg/kg for individuals with TSH levels between 1.0 and 2.0 mIU/mL, and 1 µg/kg for patients with a TSH above 2.0 mIU/mL. In turn, the dose of selenomethionine (200 µg 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 for first two months and then every 4 weeks thereafter. Compliance was be 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 performed three times: before treatment and after three and six months of levothyroxine and/or selenomethionine administration..We determined plasma levels of TSH, free thyroxine and free triiodothyronine, plasma thyroid peroxidase and thyroglobulin antibodies, lipid profile, plasma glucose and insulin and plasma high sensitivity C-reactive protein levels (hsCRP), as well as monocyte release of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), and lymphocyte release of TNF-alpha, interleukin-2, interferon-gamma.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 32285 0
Address 32285 0
Country 32285 0
Phone 32285 0
Fax 32285 0
Email 32285 0
Contact person for public queries
Name 15532 0
Robert Krysiak (principal investigator), MD, PhD
Address 15532 0
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, PL 40-752 Katowice, Poland
Country 15532 0
Poland
Phone 15532 0
+48 32 2523902
Fax 15532 0
+48 32 2523902
Email 15532 0
r.krysiak@interia.pl
Contact person for scientific queries
Name 6460 0
Robert Krysiak (principal investigator), MD, PhD
Address 6460 0
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, PL 40-752 Katowice, Poland
Country 6460 0
Poland
Phone 6460 0
+48 32 2523902
Fax 6460 0
+48 32 2523902
Email 6460 0
r.krysiak@interia.pl

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary