Clinical trial NCT02013479: Selenium Supplementation in Autoimmune Thyroiditis
Official title: The Chronic Autoimmune Thyroiditis Quality Of Life Selenium Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autoimmune Thyroiditis
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Bispebjerg Hospital
name: Esbjerg Hospital - University Hospital of Southern Denmark
name: Pharma Nord
name: The Danish Medical Research Council
name: Region of Southern Denmark
name: University of Southern Denmark
First posted: 2013-12-17
Enrollment: 415
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Our aim is to investigate if selenium supplementation versus placebo adjuvant to the standard treatment with levothyroxine (LT4) in patients with autoimmune thyroiditis will lead to improved thyroid specific quality of life, and reduced autoimmune activity. The trial will include 472 participants (2 X 236) from four clinical trial sites.

Detailed description: Background: Chronic autoimmune thyroiditis (AIT) is a common autoimmune disease that often leads to impaired function of the thyroid gland, increases in incidence with age, and has an 8-9 time female preponderance. Quality of life is often impaired and complaints persist in a considerable number of patients, even after restoration of euthyroidism. The autoimmune component of the disease has been suggested as an explanation for this. Selenium is a micro nutritive essential for human health and the thyroid gland has the highest selenium concentration of all human tissues. Selenoproteins catalyse thyroid hormone metabolism and anti-oxidative processes in thyrocytes. In addition they are important to immune function. In Denmark, patients with AIT have lower blood selenium concentration than the background population. The majority of 13 randomised trials have shown that selenium supplementation decreases serum thyroid peroxidase antibody levels (TPO-Ab) in patients with AIT, when compared with placebo. We hypothesise that adjuvant selenium may be beneficial in the treatment of AIT.

Objectives: To investigate if selenium supplementation versus placebo adjuvant to the standard treatment with levothyroxine (LT4) in patients with AIT will lead to improved thyroid specific quality of life, and reduced autoimmune activity.

Design and trial size: The CATALYST trial is an investigator-initiated randomised, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with AIT. The trial will include 472 participants (2 X 236) from four clinical trial sites.

Intervention and duration: The experimental intervention group will receive 200 μg selenium-enriched yeast as two oral tablets once daily for 12 months. The control group will receive two placebo tablets, identical in appearance, taste and smell, once daily for 12 months. Six months additional follow-up leads to a trial duration of 18 months. The experimental supplement will be SelenoPrecise® by Pharma Nord ApS.

Time schedule: July 2012 - February 2014: preparation, approval and trial registration . March 2014: first participant first visit. March 2016: last participant first visit. September 2017: last participant last visit. Autumn 2017: analysis of biological samples and data, preparation of manuscripts.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years.
2. Serum-TPO-Ab ≥ 100 IU/mL measured within the last 12 months.
3. Receiving LT4 treatment.

   - Serum-TSH ≥ 4.0 mU/L measured prior to treatment initiation
4. Written informed consent.

Exclusion Criteria:

1. Previous diagnosis of toxic nodular goitre, Graves' hyperthyroidism, post-partum thyroiditis or thyroid associated orbitopathy (TAO).
2. Previous radioiodine therapy, anti-thyroid treatment or thyroid surgery.
3. Previous diagnosis of non-melanoma skin cancer.
4. Morbidity, rendering the participant unable to process patient reported outcomes or receive intervention during the trial.
5. Systemic immunomodulatory medication.
6. Other medication known to affect thyroid function.
7. Pregnancy, breastfeeding, or planned pregnancy within 18 months.
8. Allergy towards the components in the selenium or placebo pills.
9. Intake of selenium supplementation ≥ 55 μg/d.
10. Unable to read or understand Danish.
11. Lack of informed consent

Primary outcomes:
measure: Thyroid related quality of life
timeFrame: 12 months after initation of intervention
Secondary outcomes:
measure: Thyroid peroxidase antibody concentration (TPO-Ab)
timeFrame: 12 months after initation of intervention
measure: Levothyroxine (LT4) dosage
timeFrame: 12 months after initation of intervention
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Clinic of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet
city: Copenhagen
country: Denmark
facility: Department of Endocrinology and Gastroenterology, Bispebjerg Hospital
city: Esbjerg
country: Denmark
facility: Department of Internal Medicine, Hospital of South West Denmark
city: Odense
country: Denmark
facility: Department of Endorcrinology and Metabolism, Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Steen J Bonnema, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Laszlo Hegedüs, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Kristian H Winther, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Torquil Watt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Per Cramon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Ulla Feldt-Rasmussen, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Åse K Rasmussen, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Esbjerg Hospital - University Hospital of Southern Denmark
name: Jeppe Gram, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bispebjerg Hospital, Denmark
name: Nils J Knudsen, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Winther KH, Watt T, Bjorner JB, Cramon P, Feldt-Rasmussen U, Gluud C, Gram J, Groenvold M, Hegedus L, Knudsen N, Rasmussen AK, Bonnema SJ. The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial. Trials. 2014 Apr 9;15:115. doi: 10.1186/1745-6215-15-115.