Melanocortin Gene Expression in Lymphocytes of Polymyalgia Patients

January 11, 2023 updated by: Michael Kruse Meyer, Aalborg University

Is the Melanocortin System Involved in Inflammatory Resolution

Polymyalgia rheumatica (PMR) is a systemic inflammatory disorder with unknown etiology and overlapping symptoms with giant cell arthritis and rheumatoid arthritis (RA). The proteomic profile of PMR patients remains uncharacterized and biomarker studies very limited. The primary aim of this study was to thoroughly investigate the lymphocyte expression of melanocortin receptors, and the serum proteome during glucocorticoid treatment of PMR with a focus on acute-phase reactions, the complement system, and pro-inflammatory cytokines.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Polymyalgia rheumatica (PMR) is a prototypic systemic inflammatory disease with overlapping symptoms similar to late onset rheumatoid arthritis (RA), giant cell arthritis (GCA), and cancer [1]. The etiology of PMR remains largely unknown, but it has been suggested that an age-related decline in the adaptive immune system might play a role in an over-compensatory inflammatory innate immune response [2]. Some genes and polymorphisms involved in initiation and regulation of inflammation have been associated with PMR [3,4] and polymorphisms are more predominant in the Northern European than Mediterranean population [5]. PMR has been somewhat successfully treated with glucocorticoids (e.g. prednisone) for more than half a century [6]. Due to the lack of causative molecular knowledge about the driving factors of inflammatory activation, and lack of treatment alternatives, glucocorticoids are still applied as the first line treatment today [7]. Relapses are common during standard glucocorticoid treatment [8], and randomized trials have failed to provide new treatment options [9,10]. However, recent progress in GCA treatment [11] have paved the way for biological treatment of PMR.

Only few serological biomarkers have been associated to PMR pathogenesis and disease activity while the pathogenesis of RA has been more thoroughly investigated. Hence, there is an unmet need to elucidate the pathophysiology of PMR. In this pilot-study, we therefore explored the potential to identify new serological markers at disease onset, which could be responsive to glucocorticoid treatment, which could be linked to PMR pathology. We did this using state-of-the-art quantitative proteomics profiling to investigate serum proteins from PMR patients before and after treatment with glucocorticoids for three months. In addition, we compared these patients with DMARD naïve RA patients, and healthy controls for potential molecular similarities. Hence, we applied advanced, qPCR to investigate lymphocyte expression, and mass spectrometry (MS) to measure serum proteins, and compared the results with serum cytokines.

Study Type

Observational

Enrollment (Actual)

9

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

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The inclusion criteria ensured that the PMR patients had a high disease activity. After three months, the patients had obtained significant effect of the glucocorticoid treatment evaluated by physical examinations and clinical biochemistry values (Table 1).

Description

Inclusion Criteria:

  • The PMR diagnosis fulfilled the ACR 1987 criteria [20]. Additional inclusion criteria were elevated CRP, and sedimentation rate, ultrasound verified synovitis [21], and ].

Exclusion Criteria:

  • no cancer related findings on computed tomography (CT) of the abdomen, and chest X-ray to increase specificity as described by ACR 2012 classification criteria [22

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: Case-Only
  • Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Melanocortin receptor expression
Time Frame: 3 months.
Melanocortin receptor expression determined like previously: https://pubmed.ncbi.nlm.nih.gov/27434862/
3 months.
Serum proteome
Time Frame: 3 months.
Mass spectrometry investigated serum proteome
3 months.

Collaborators and Investigators

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

Sponsor

Aalborg 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 (Actual)

March 1, 2012

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2022

Study Registration Dates

First Submitted

December 28, 2022

First Submitted That Met QC Criteria

January 11, 2023

First Posted (Actual)

January 12, 2023

Study Record Updates

Last Update Posted (Actual)

January 12, 2023

Last Update Submitted That Met QC Criteria

January 11, 2023

Last Verified

December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N-20120074

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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