Development of a Novel Human In Vitro Sarcoidosis Model

Completed

• Conditions: Sarcoidosis
• Interventions: Other: No intervention, observational study only

• Registration Number: NCT01857401
• Lead Sponsor: Elliott Crouser MD

Brief Summary

There is currently no experimental model that accurately represents sarcoidosis. The lack of a useful research model significantly slows progress towards developing new treatments for sarcoidosis. The investigators plan to develop a new model for sarcoidosis research and will test the model to see if it helps us understand how sarcoidosis develops and if it is useful for testing new treatments.

Detailed Description

Sarcoidosis is a systemic granulomatous disease of unknown cause, most commonly affecting the lungs, which tends to afflict young adults in the prime of their lives. Recent data indicating that sarcoidosis mortality rates are rising in the U.S. (1) and Europe (2) highlight the inadequacy of current therapies. As noted in a recent NIH-sponsored sarcoidosis workshop, the lack of relevant animal, computer or in vitro models represents a bottleneck for progress towards understanding disease mechanisms and developing highly effective sarcoidosis treatments (3). The lack of useful disease models likely contributes to the current lack (zero) of investigator-initiated (RO1) projects supporting sarcoidosis research.

The long-term goal of this proposal is to develop a novel human sarcoidosis research model to fill the current void in the field, thereby expediting exploration of basic disease mechanisms and pre-clinical testing of novel therapies. The objective of this application, which is the first step towards achieving the long-term goal, is to develop a novel in vitro human granuloma model to represent abnormal granuloma formation in the context of sarcoidosis. In this regard, a growing body of evidence indicates that mycobacterial antigens are commonly harbored in sarcoidosis tissues, to which these patients are sensitized (4, 5). Our central hypothesis is that the pathological mechanisms of sarcoidosis can be modeled in vitro, as represented by abnormal granuloma formation in response to mycobacterial and other ubiquitous environmental antigens. The feasibility of our proposed model is supported by preliminary studies showing that subjects sensitized to Mycobacterium tuberculosis antigens (latent TB tuberculosis with a positive TB skin test) form well-organized granulomas readily in response to challenge with TB antigens, compared to healthy controls. This project is highly innovative and we feel has an excellent likelihood of leading to a critical breakthrough in the field of sarcoidosis research.

Study Timeline

• Study Start: 2012-12-19
• Study First Submitted: 2013-05-02
• Study First Submitted QC: 2013-05-15
• Study First Posted: 2013-05-20
• Primary Completion: 2017-02-02
• Study Completion: 2017-02-02
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-01
• Last Update Posted: 2021-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• sarcoidosis, subjects (18 - 45 years of age), including 30 sarcoidosis, 15 latent TB and 15 healthy controls.

Exclusion Criteria

• pregnant women

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational study	No intervention, observational study only	Blood draw only, observational study

Primary Outcome Measures

Name	Time	Method
Sarcoidosis patients, volunteers with latent TB, and healthy volunteer subjects will be recruited to donate peripheral blood for isolation of peripheral blood mononuclear cells.	2-4 years	We hypothesize that patients with the active sarcoidosis phenotype will exhibit accelerated granuloma formation with higher IL-10(IL Interleukin)and IL-4 expression relative to patients with the self-limited sarcoidosis phenotype

Trial Locations

Locations (1)

Biomedical Research Tower, 10th floor; 🇺🇸 Columbus, Ohio, United States