Incidence of Cereblon in Intensive Care Patients

October 6, 2021 updated by: Pınar Ayvat, Buca Seyfi Demirsoy State Hospital

Classical immunomodulatory drugs (IMiDs) like thalidomide and its second- and third-generation analogues lenalidomide, pomalidomide, avadomide (CC-122), and iberdomide (CC-220) have constantly emerged to new therapeutic areas. Originally developed as a sedative and banned in 1961 for its teratogenic effects when used during pregnancy, thalidomide and a number of newly developed analogues are approved for the treatment of multiple myeloma (MM),4 erythema nodosum5 and myelodysplastic syndrome (MDS) Thalidomide was used as a treatment for morning sickness from 1957 until 1961 but was withdrawn from the market after it was discovered that it caused birth defects. Because of their pleiotropic and especially anti-angiogenic properties, IMiDs have further been reported effective in many off-label indications as for Hodgkin's lymphoma, light chain-associated (AL) amyloidosis, and acute myeloid leukemia (AML).

The drug thalidomide binds to cereblon and changes which substrates can be degraded by it, which leads to an antiproliferative effect on myeloma cells and possibly the teratogenic effect on fetal development. The idea that cereblon modulation is responsible for the teratogenic activity of thalidomide in the chick and zebrafish was cast into doubt due to a 2013 report that pomalidomide (a more potent thalidomide analog) does not cause teratogenic effects in these same model systems even though it binds with cereblon more strongly than thalidomide.

Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex. Several key findings suggest diverse roles of CRBN, including its regulation of the large-conductance calcium- and voltage-activated potassium (BKCa) channels, regulation of thalidomide-binding proteins, and mediation of lenalidomide treatment in multiple myeloma. Recent studies also indicate that CRBN is involved in energy metabolism and negatively regulates AMP-activated protein kinase signaling. Recent studies also indicate that CRBN is involved in energy metabolism and negatively regulates AMP-activated protein kinase signaling. Mice with genetic depletion of CRBN are resistant to various stress conditions including a high-fat diet, endoplasmic reticulum stress, ischemia/reperfusion injury, and alcohol-related liver damage.

There are different drugs that have an immunomodulating effect, such as thalidomide analogs, and are used in various situations. Some of the diseases in which the immune system plays a role in its etiology are Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury (ALI), septic shock, and sepsis. In cases of lung injury such as sepsis, septic shock, ARDS, ALI, the immune system is over-activated and as a result, the immune system cells damage the own tissue of the lung. To break this mechanism, immunomodulatory drugs are used in intensive care in the treatment of these diseases.

There is no publication regarding the role of Cereblon in the mechanism of action of these immunomodulatory drugs used in intensive care. In these intensive care diagnoses (sepsis, ARDS, ALI), there is no publication showing the correlation between the severity of the disease and Cereblon protein. Other laboratory parameters are used to estimate the effects (mortality and morbidity) of these diseases on the patient. At the end of the investigators study, the investigators think that the Cereblon gene can be used in this estimation of mortality or morbidity.

Study Overview

Status

Not yet recruiting

Conditions

Study Type

Observational

Enrollment (Anticipated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

critical care patient

Description

Inclusion Criteria:

  • Being over 18 years old,
  • Having (-) Covid PCR test,
  • Being intubated,
  • Getting permission from the patient's relatives to be included in the study

Exclusion Criteria:

  • Being under the age of 18,
  • Having (+) Covid PCR test,
  • Not be able to get consent from the relatives of the patient

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

  • Observational Models: Other
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
critical care patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The presence of Cereblon protein
Time Frame: until 31 December 2021
To demonstrate the presence of Cereblon protein in tracheal aspiration fluid from intensive care patients.
until 31 December 2021

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The relationship between Cereblon and intensive care length of stay
Time Frame: until 31 December 2021
To determine whether there is a relationship between the presence of Cereblon protein and the length of stay in the intensive care unit.
until 31 December 2021

Collaborators and Investigators

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

Sponsor

Buca Seyfi Demirsoy State Hospital

Investigators

  • Study Chair: Pınar Ayvat, ass. prof., Izmir Democracy University

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.

General Publications

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 (Anticipated)

December 1, 2021

Primary Completion (Anticipated)

February 1, 2022

Study Completion (Anticipated)

April 1, 2022

Study Registration Dates

First Submitted

September 24, 2021

First Submitted That Met QC Criteria

October 6, 2021

First Posted (Actual)

October 19, 2021

Study Record Updates

Last Update Posted (Actual)

October 19, 2021

Last Update Submitted That Met QC Criteria

October 6, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Cereblon

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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