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Interaction Between Levothyroxine and Probiotics in Hypothyroid Patients

Not Applicable
Completed
Conditions
Hypothyroidism
Interventions
Other: a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®)
Registration Number
NCT03095963
Lead Sponsor
Azienda USL Modena
Brief Summary

A prospective, randomized, single-blind, controlled, investigator-started clinical trial was carried out. Patients with primary hypothyroidism were randomly assigned to the study (VSL#3®+ LT4) and the control group (LT4). A two months treatment phase was followed by two months of follow-up. Clinical examination, blood tests for thyroid function and for peripheral tissue markers of thyroid hormones effect were performed monthly for 4 months. LT4 dose adjustments were performed during the study when necessary.

Detailed Description

Consecutive patients on LT4 replacement therapy attending the Endocrinology Unit of Modena (Italy) were screened. According to inclusion and exclusion criteria, eighty participants were enrolled and randomized in study or control group. The random allocation sequence was generated using 'Statistical Package for the Social Sciences' software for Macintosh (SPSS) considering a 1:1 ratio by the statistician of the Unit. Clinicians evaluating and enrolling patients were blinded to the randomization list. The study design provided a monthly visit for a 4 months overall time-frame. Patients assigned to the study group took the probiotic supplement VSL#3® for two months, followed by a two months period of follow-up. Study group patients were taught to assume the probiotic supplement at least two hours after LT4 administration, to dissolve it in a cold beverage and to store it in a refrigerator (2°-8°C) in order to preserve bacteria load. The study design was single-blind since only the clinician was aware of the allocation. The VSL#3® administration was provided by nurses. Participants were invited to return all used and unused sachets to count the number of opened sachets per the number of treatment days.

All patients underwent five visits (baseline, visit 1, 2, 3 and 4) in which anthropometrical evaluation (weight and height) and hormonal function assessment were performed. A blood sample was taken in the morning at each visit, on empty stomach and before LT4 ingestion. In occurrence of hormonal alteration, LT4 daily dose was adjusted according to clinical guidelines. At baseline, visit 2 and visit 4, patients underwent clinical examination with heart rate and blood pressure evaluation. During each visit, the following data were collected: probiotic assumption, sex, age, hypothyroidism aetiology, LT4 formulation dose and brand, body mass index (BMI), body surface area (BSA), systolic blood pressure, diastolic blood pressure, heart rate, TSH, fT4, fT3 and any possible LT4 posology adjustment. All the clinical data have been further databased.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
Inclusion Criteria
  • primary hypothyroidism on LT4 replacement therapy
  • TSH, fT3 and fT4 in the normal range
  • stable LT4 dosage during the previous six months before enrolment
  • Caucasian ethnicity
Exclusion Criteria
  • total thyroidectomy for thyroid carcinoma
  • high fiber diet
  • intestinal malabsorption (e.g. bariatric surgery, inflammatory bowel diseases, coeliac disease)
  • ongoing therapies interfering with LT4 absorption and/or metabolism (i.e. aluminium-containing antacids, sucralfate, proton pump inhibitors, calcium carbonate, raloxifene, bile acids sequestrants and ferrous sulfate)
  • antibiotics treatment in the previous six months before enrolment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Probioticsa mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®)The study group took a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®) in addition to levothyroxine
LevothyroxinelevothyroxinThe control group took levothyroxine only
ProbioticslevothyroxinThe study group took a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®) in addition to levothyroxine
Primary Outcome Measures
NameTimeMethod
differences in thyroid-stimulating hormone (TSH) serum levels comparing study group and controlsThrough study completion, an average of 4 months

measurement of serum levels of thyroid-stimulating hormone (TSH) - unit of measure: microIU/mL, normal range: 0.35-4.94

Secondary Outcome Measures
NameTimeMethod
differences in thyroid hormones by biochemical assays comparing study group and controlsThrough study completion, an average of 4 months

measurement of serum levels of free triiodothyronine (fT3) - unit of measure: pg/mL, normal range: 1.7-3.7; measurement of serum levels of free thyroxine (fT4) - unit of measure: pg/mL, normal range: 7-15

differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controlsThrough study completion, an average of 4 months

measurement of serum levels of angiotensin-converting enzyme (ACE) - unit of measure: U/L, normal range: 8-52

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