Interaction Between Levothyroxine and Probiotics in Hypothyroid Patients

March 24, 2017 updated by: Manuela Simoni, Azienda USL Modena

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
differences in thyroid-stimulating hormone (TSH) serum levels comparing study group and controls
Time Frame: Through 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
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
Time Frame: Through study completion, an average of 4 months
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
Time Frame: Through study completion, an average of 4 months
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
Time Frame: Through study completion, an average of 4 months
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
Time Frame: Through study completion, an average of 4 months
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
Time Frame: Through study completion, an average of 4 months
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
Time Frame: Through study completion, an average of 4 months
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
Time Frame: Through 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
Through study completion, an average of 4 months
differences in thyroid hormones by biochemical assays comparing study group and controls
Time Frame: Through 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
Through study completion, an average of 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

October 25, 2016

Study Completion (Actual)

October 25, 2016

Study Registration Dates

First Submitted

March 15, 2017

First Submitted That Met QC Criteria

March 24, 2017

First Posted (Actual)

March 30, 2017

Study Record Updates

Last Update Posted (Actual)

March 30, 2017

Last Update Submitted That Met QC Criteria

March 24, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Other Study ID Numbers

  • Levothyroxine and Probiotics

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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