Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04784364 |
| Other study ID # |
HSM 20-01252 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 3, 2021 |
| Est. completion date |
March 2026 |
Study information
| Verified date |
December 2023 |
| Source |
Icahn School of Medicine at Mount Sinai |
| Contact |
Sarah Alvi |
| Phone |
212-659-9416 |
| Email |
Sarah.Alvi[@]mssm.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The study team plans to establish a bioregistry of patients receiving biologic therapy as
part of their standard treatment at the Mount Sinai Therapeutic Infusion Center and
affiliated practices. The study team will to apply state-of-the-art approaches to assessing
and predicting immunological and clinical responses associated with these standards and
prescribed treatments. The approach is twofold. The first component is to establish a robust
and flexible biorepository and database that includes demographic, immunologic, exposure and
clinical records, and can facilitate research across disciplines, and across other registries
affiliated with Mount Sinai. The second component is to address specific key research
questions focused on using novel diagnostics to increase the effectiveness of biologic
treatment. Most patients will be recruited from the Mount Sinai Therapeutic Infusion Center
(TIC), although others receiving infusions elsewhere or at home will be recruited from
outpatient Sinai affiliated clinical practices.
Description:
The study team proposes a twofold approach to determine how immunophenotype may affect the
course of clinical immunological disease for patients receiving biologic therapy. First, the
team intends to establish a biorepository and database that includes demographic,
immunologic, exposure and clinical records. The registry will be set up to facilitate
research across disease disciplines, and across other registries affiliated with ISMMS.
Second, over time, the team aims to address specific and an increasing number of research
questions focused on using novel diagnostics to increase the effectiveness of biologic
treatment as outlined below. Most subjects will be recruited from the Mount Sinai Therapeutic
Infusion Center (TIC), although others receiving infusions elsewhere or at home will be
recruited from outpatient affiliated clinical practices during scheduled medical visits.
Specific Aims:
1. (Overarching) Build a repository of biological specimens, questionnaire data, and apply
state-of-the-art assessment tools to assess the current immunological and clinical condition,
and changes over time. Specimens and data will be collected in a manner that can readily
incorporate new technology, new research questions, link to intelligent analytics, and
provide a resource for future consortia across disciplines. An infrastructure will be created
that includes a multi-disciplinary Steering Committee to facilitate spinoff research studies
and harmonize protocols within the TIC and across the Sinai system, resolve procedural
questions, and communicate updated policies to referring physicians.
Additional initial specific scientific aims related to responses to biologics prescribed as
part of standard practice that will be considered in this proposal are to determine:
2 . Effects of anti-IgE therapy on IgE phenotypes, maturation and production, and clinical
outcomes.
3. Effects of anti-IgE and anti-IL-5 therapies on dopaminergeric pathways and clinical
outcomes.
4. Effects of anti-TNF, anti-CD20, and other biologic therapies on immunological and clinical
outcomes.
5. Effects of IVIG therapy on immunological and clinical course in Common Variable Immune
Deficiency.
Futures studies will focus on Clinical Decision Support (CDS), Artificial Intelligence, and
use of technology to inform and educate current TIC patients. Future studies also will
feature studies related to immunological and clinical responses to additional biological
therapies.
Background The prescription of biological agents and immune modulators to treat chronic
immunological-based diseases continues to expand. This trend is predicted to continue.
Applying data-driven and immunophenotype-driven approaches to their use could reveal
additional pharmacologic targets and signal disease presence or relapse prior to the onset of
clinical symptoms. These advances in precision medicine also may reduce adverse drug
reactions and help control overall cost of healthcare associated with inefficient and 'trial
and error' prescribing. They also may provide information on susceptible individuals and
their appropriate care during healthcare crises, such as the current COVID-19 pandemic.
Despite these developments, prospective studies and clinical trials that feature
immunophenotyping to facilitate 'real world' therapeutic decision-making are limited. More
comprehensive immunophenotyping has predicted clinical responses to cancer immunotherapy,
suggesting that this approach may translate to immunologically-mediated nonmalignant
diseases. But widespread application to multiple chronic diseases is limited by several
research gaps. These include determination of: 1) new biomarkers (discovery, validation) that
may inform clinicians of drug responsive endotypes, 2) biomarkers that predict disease course
over time in replicate studies, 3) optimal methods to link immunophenotype with analytic
diagnostic and clinical decision-making tools to predict disease course, 4) factors that
mediate treatment responses, some of which may be modifiable (eg environmental exposures,
viruses, disease phenotypes).
The Mount Sinai Therapeutic Infusion Center is an ideal location where investigators have the
potential to fill in many of these research gaps. The volume is large, with currently 1803
individuals actively (in 2019) receiving anti-cytokine or anti-CD20 biological treatment for
their immunological, dermatological and neurological disorders, largely prescribed by members
of the Divisions of Clinical Immunology, Rheumatology, Pulmonary, Inflammatory Bowel Disease
(IBD), Neurology and Dermatology. Further, investigators across Divisions (Clinical
Immunology, Rheumatology, IBD) and Departments (Medicine, Neurology, Dermatology) have
created a research working group to discuss collaborations and standardized approaches to
assessing immunological responses to biologics. This registry also intends to coordinate with
other registries at ISMMS to ensure that it utilizes common approaches to biomonitoring and
common data elements as much as feasible to facilitate comparisons across cohorts.
Primary and Secondary Study Endpoints
The initial scientific hypotheses focus on these endpoints:
Aim 1 An expanded repository of biological specimens and questionnaire data.
Aim 2 Measures of IgE phenotypes and associated clinical airway outcomes.
Aim 3 Measures of changes in the dopaminergic pathway and clinical airway outcomes.
Aim 4 Measures of anti-TNF, anti-CD20, and other biologic therapies on immunological and
clinical outcomes.
Aim 5 Measures of IVIG-induced immunological and clinical outcomes.
