Interaction Between Levothyroxine and Probiotics in Hypothyroid Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Probiotics Assumption on Serum Thyroid Hormone and TSH Levels in Hypothyroid Patients on Levothyroxine Treatment

Conditions
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Hypothyroidism

Intervention / Treatment
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* Other: a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®)
* Drug: levothyroxin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotics<br>The study group took a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®) in addition to levothyroxine | Other: a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®)<br>* Patients assigned to the study group took the probiotic supplement VSL#3® for two months, in addition to levothyroxine<br>Drug: levothyroxin<br>* replacement therapy for hypothyroidism<br>|
| Active Comparator: Levothyroxine<br>The control group took levothyroxine only | Drug: levothyroxin<br>* replacement therapy for hypothyroidism<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differences in thyroid-stimulating hormone (TSH) serum levels comparing study group and controls | measurement of serum levels of thyroid-stimulating hormone (TSH) - unit of measure: microIU/mL, normal range: 0.35-4.94 | Through study completion, an average of 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controls | measurement of serum levels of total cholesterol (CH) - unit of measure: mg/dL, normal range: <200 | Through study completion, an average of 4 months | 
| differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controls | measurement of serum levels of sex hormone-binding globulin (SHBG) - unit of measure: nmol/L, normal range: males 13.5-71.4, females 19.8-155.2 | Through study completion, an average of 4 months | 
| differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controls | measurement of serum levels of ferritin - unit of measure: ng/mL, normal range: 25-400 | Through study completion, an average of 4 months | 
| differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controls | measurement of serum levels of creatine phosphokinase (CPK) - unit of measure: U/L, normal range: 10-71 | Through study completion, an average of 4 months | 
| differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controls | measurement of serum levels of myoglobin - unit of measure: ng/mL, normal range: 15-106 | Through study completion, an average of 4 months | 
| differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controls | measurement of serum levels of osteocalcin - unit of measure: ng/mL, normal range: 4.6-65.4 | Through study completion, an average of 4 months | 
| differences in peripheral tissue markers of thyroid hormones by biochemical assays comparing study group and controls | measurement of serum levels of angiotensin-converting enzyme (ACE) - unit of measure: U/L, normal range: 8-52 | Through study completion, an average of 4 months | 
| differences in thyroid hormones by biochemical assays comparing study group and controls | 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 | Through study completion, an average of 4 months |