NCT02373995

Brief Summary

Graves' orbitopathy (GO), also known as thyroid eye disease, affects approximately 3 million people in Europe with an estimated socioeconomic burden of 6.4 billion euros per annum. GO is a complication of Graves' disease which is an autoimmune disease and the commonest cause of an overactive thyroid gland. The treatment of GO remains unsatisfactory and the majority of patients report long-term impairment of quality of life. The effects of gut derived antigens, from micro-organisms and nutrients, on the autoimmune response will be tested in the animal model by probiotic and "contra-biotic" intervention. In the Indigo interventional trial the investigators will add to the standard anti-thyroid drug treatment (ATD) a specifically designed probiotics (LAB4, Cultech Ltd., West Glamorgan, UK) to assess whether it is possible to modify the microbiome in GD patients and improve their immunological status.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Feb 2015

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 29, 2015

Completed
3 days until next milestone

Study Start

First participant enrolled

February 1, 2015

Completed
26 days until next milestone

First Posted

Study publicly available on registry

February 27, 2015

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

February 27, 2015

Status Verified

February 1, 2015

Enrollment Period

5 months

First QC Date

January 29, 2015

Last Update Submit

February 26, 2015

Conditions

Graves' Disease

Keywords

GravesOrbithopatyeuthyroidismmicrobiome

Outcome Measures

Primary Outcomes (1)

  • Microbiome modification (beneficial modification of the gut microbioma relates to a reduction at the end of treatment of at least 5% of the Firmicutes:Bacteroides ratio and 30% of the anti-TSHr antibody titer and of total IgG and IgA concentrations)

    modification the microbiome in GD patients to reduce pathogenic species and enrich its commensal, symbiotic components. The proportion (%) of each species will be assessed and recorded.

    6 months

Secondary Outcomes (1)

  • Improvement immunological status (antibody responses will be analyzed to identify if microbial or food derived antigens are involved in triggering disease or associated with GO progression)

    6 months

Study Arms (2)

LAB4

ACTIVE COMPARATOR

In addition to conventional Anti Thyroid Drug (ATD), LAB4 probiotic preparation will be administered at the 2 cps x 2/die dosing with food for 6 months. It is key to properly store LAB4 at 8°C.

Biological: LAB4

Placebo

PLACEBO COMPARATOR

In addition to conventional Anti Thyroid Drug (ATD) a LAB4 placebo preparation will be administered at the 2 cps x 2/die dosing with food for 6 months. It is key to properly store placebo at 8°C.

Interventions

LAB4BIOLOGICAL

Additional treatment with the specific LAB4 probiotic preparation

LAB4

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Group A: Untreated Graves' hyperthyroidism (or within 4 weeks of initiating ATD treatment)
  • definition hyperthyroidism: TSH decreased, FT4 and /or FT3 increased
  • definition Graves': diffusely enlarged thyroid gland either by palpation or echograpy, and/or homogeneous thyroid uptake at scintigraphy, or positive TSHRAb
  • first episode or recurrence of Graves' hyperthyroidism
  • minimal or no eye signs, defined as lid retraction / lid lag but no other signs.
  • Planned treatment with antithyroid drugs either titration regimen or block-and-replace regimen for 18 months.
  • Group B. Untreated Graves' hyperthyroidism (or within 4 weeks of initiating ATD treatment) with overt signs of GO as defined by EUGOGO1
  • Mild GO: patients whose features of GO have only a minor impact on daily life insufficient to justify immunosuppressive or surgical treatment. They usually have only one or more of the following: minor lid retraction (\<2 mm), mild soft tissue involvement, exophthalmos \<3 mm above normal for race and gender, transient or no diplopia, and corneal exposure responsive to lubricants)
  • Moderate-to-severe GO: Patients without sight-threatening GO whose eye disease has sufficient impact on daily life to justify the risks of immunosuppression (if active) or surgical intervention (if inactive). Patients with moderate-to-severe GO usually have any one or more of the following: lid retraction R2 mm, moderate or severe soft tissue involvement, exophthalmos \>3 mm above normal for race and gender, inconstant, or constant diplopia.
  • Sight -threatening GO: Patients with dysthyroid optic neuropathy (DON) and/or corneal

You may not qualify if:

  • Previous or planned treatment with 131I or thyroidectomy (A\&B); sight threatening GO requiring decompression (B); drugs interfering with the natural course of GO (A\&B): steroids, immunosuppressants, thiazolidinediones, antibiotics / antifungals / antivirals (both topical and systemic for at least 4 weeks prior to recruitment to the study); acute diarrhea illness (gastroenteritis for at least 4 weeks prior to recruitment to the study); Drugs interfering with thyroid function (A\&B): amiodarone, lithium, iodine supplements; Drug or alcohol abuse (A\&B); no informed consent (A\&B); Age less than 18 (A\&B); Pregnancy (A\&B).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fondazione Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Related Publications (1)

  • Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Curro N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marino M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM; European Group on Graves' Orbitopathy (EUGOGO). Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008 Mar;158(3):273-85. doi: 10.1530/EJE-07-0666. No abstract available.

    PMID: 18299459RESULT

MeSH Terms

Conditions

Graves Disease

Condition Hierarchy (Ancestors)

ExophthalmosOrbital DiseasesEye DiseasesGoiterThyroid DiseasesEndocrine System DiseasesHyperthyroidismAutoimmune DiseasesImmune System Diseases

Study Officials

  • Mario Salvi, MD

    IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Mario Salvi, MD

CONTACT

+393487362498mario@mariosalvinet.it

Giuseppe Colucci, MD

CONTACT

+393486510071coluccg1@gmail.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 29, 2015

First Posted

February 27, 2015

Study Start

February 1, 2015

Primary Completion

July 1, 2015

Study Completion

December 1, 2016

Last Updated

February 27, 2015

Record last verified: 2015-02

Locations

IT(1)