Clinical trial NCT02653079: Immunophenotyping From Blood of Patients Suffering From Chronic Degenerating Joint Diseases and Receiving LDRT
Official title: Immunophenotyping From Blood of Patients Suffering From Chronic Degenerating Joint Diseases and Receiving Local Low Dose Radiation Therapy (LDRT)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Inflammatory Disorder
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2016-01-12
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients suffering from chronic inflammatory diseases of the joints, namely painful shoulder syndrome (periarthritis humeroscapularis), painful elbow syndrome (Epicondylopathia humeri), benign achillodynia, benign calcaneodynia, arthosis (finger- , rhiz-, gon-, and anklearthrosis, and arthritis (gon- and anklearthrosis).

Patients were attributed to our clinic and the study protocol was explained in detail. The patients have to give their informed consent before starting with the LDRT. The treatment-plan of the underlying disease remained unchanged. This treatment scheme is conducted with 2 irradiations within 7 days for total treatment duration of 3 weeks. The single dose is 0.5 Gy and the complete dose of one round of LDRT is 3 Gy.

Brief summary: Patients suffering from chronic degenerating diseases are often treated by a plethora of NSAIDs, DMARDs, Biologicals, as well as combinations of these therapeutics. However, many patients are refractory to this treatment and suffer from chronic pain over years, leading to a worsening of the quality of live. The mobilization of these patients is one main goal in the therapy of these chronic and inflammatory diseases. Low dose radiation therapy (LDRT) is applied since more than one century for the local treatment of chronic degenerating joint diseases. The success of the treatment was described by many retrospective as well as pattern of care studies, respectively.

Local (only at the painful joint) low dose irradiation of the chronic patients results in most patients in a significantly reduced pain, not only direct after the therapy, but also lasting for more than 12 month in many cases. The patients experience enhanced mobility and increased quality of life. The molecular and cellular processes leading to the pain reduction are just fragmentarily analyzed. Our group revealed that macrophages are key players in radiation-induced immune modulation. Inflammatory macrophages exposed to low doses of radiation showed a reduced inflammatory capacity and attenuated an inflammatory microenvironment. Besides macrophages further immune cells are most likely involved in reduction of inflammation following LD-RT, as in vitro already shown for neutrophils.

The IMMO-LDRT01 study aims for the first time to analyze in detail the immune status of patients suffering from inflammatory, chronic joint diseases before, during and after LD-RT in a longitudinal manner. The multi-color flow cytometry-based assay will allow determining over 30 immune cell subsets and additionally their activation status. Further, biodosimetry will be performed with the whole-blood samples to get hints about dose that the immune cells are exposed to. This will be performed with national and international co-operation partners.

The IMMO-LDRT01 study is a prospective and observational study not influencing the standard therapeutic scheme and will provide hints how the LDRT affects besides local cells in the irradiated area also the systemic inflammatory response.


Eligibility criteria: Inclusion Criteria:

* Patients suffering and diagnosed for:
* painful shoulder syndrome (periarthritis humeroscapularis)
* painful elbow syndrome (Epicondylopathia humeri)
* benign achillodynia
* benign calcaneodynia
* arthosis (finger- , rhiz-, gon-, and anklearthrosis
* arthritis (gon- and anklearthrosis)
* Planned local low dose radiation therapy (LDRT) at the Department of Radiation Oncology, Universitätsklinikum Erlangen.
* Age at least 18 years

Exclusion Criteria:

* patients who are suffering or had suffered from any malignant diseases
* fertile patients who refuse effective contraception during study treatment
* persistent drug and/or alcohol abuse
* patients not able or willing to behave according to study protocol
* patients in care
* patients that are not able to speak German

Primary outcomes:
measure: Change of circulating immune cells of treated patients by deep immunophenotyping.
timeFrame: up to 3 month after completion of RT
Secondary outcomes:
measure: Change of joint pain intensity of the treated patients.
timeFrame: up to 9 month after completion of RT
measure: Change of functional capacity in daily life of the treated patients
timeFrame: up to 9 month after completion of RT
measure: Change of health-related quality of life
timeFrame: up to 9 month after completion of RT
measure: description of pain quality
timeFrame: up to 9 month after completion of RT
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Radiation Oncology, Universitätsklinikum Erlangen
state: Bavaria
Study officials:
affiliation: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
name: Oliver J Ott, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
name: Udo S Gaipl, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Donaubauer AJ, Becker I, Weissmann T, Frohlich BM, Munoz LE, Gryc T, Denzler M, Ott OJ, Fietkau R, Gaipl US, Frey B. Low Dose Radiation Therapy Induces Long-Lasting Reduction of Pain and Immune Modulations in the Peripheral Blood - Interim Analysis of the IMMO-LDRT01 Trial. Front Immunol. 2021 Oct 12;12:740742. doi: 10.3389/fimmu.2021.740742. eCollection 2021.