Longitudinal Follow-up Study About Complex Regional Pain Syndrome (CRPS) Patients

NCT ID: NCT04703647

Last Updated: 2024-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

110 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-03-14

Study Completion Date

2025-12-31

Brief Summary

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Complex regional pain syndrome (CRPS) is a post-traumatic chronic pain condition characterized by pain and other symptoms typically affecting a distal limb. Relatively little is known about the prognosis of the course of CRPS .Currently there is no specific test to diagnose CRPS.

The primary objective of the study is to investigate prospectively the evolution of CRPS and the impact of the psychosocial factors on health status, recovery, quality of life, and working status of CRPS patients.

The secondary objective of the study is to measure blood parameters in CRPS patients to investigate their evolution during the course of CRPS, and maybe to identify distinctive biomarkers associate with CRPS and that could be potential candidate for diagnosis.

Detailed Description

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The first aim will be to monitor the evolution of the following parameters in CRPS patients:

* Quality of life
* Symptoms and signs of CRPS
* Severity of CRPS
* Working status
* Pain
* Disability
* Anxiety and depression
* Kinesiophobia
* Catastrophism
* Activity patterns with chronic pain during the two years follow-up. Every parameter will be evaluated with a questionnaire that allows assigning scores to each patient.

Additionally sociodemographic data will be collected to characterize the patients (age, gender, marital status, educational level). The health status, treatment and medication of the patients will also be recorded with a medical follow-up during the two years.

The aim is to know if the following parameters and their evolution:

* Sociodemographic factors,
* Pain,
* Disability,
* Anxiety and depression,
* Kinesiophobia,
* Catastrophism,
* Activity patterns with chronic pain

are associated with the recovery, which is evaluated with

* Quality of life,
* Severity of CRPS,
* And working status.

Potential associations between the different parameters will be tested (Pearson's correlation coefficient).

The second aim will be to assess, in blood samples, the expression levels of specific molecules (miRNAs and a selection of cytokines) in patients diagnosed with acute CRPS. Comparison with healthy controls will be performed at the first measurement time (T0) . In a second time, miRNAs and cytokines profiles will be compared between acute and chronic (CRPS still diagnosed 6 months after the first diagnosis) CRPS patients. The measured proteins will include: C-reactive protein, tumor necrosis factor-alpha (TNF), interleukin-2 \[IL-2\], IL-6, IL-8, IL-10, CD40 ligand (pro- and anti-inflammatory proteins associated with pain), gene related peptide (CGRP), bradykinins and substance P.

The screening, recruitment and enrolment of the patients will be done by the referring physician in daily clinical practice, during the consultation.

The physician will explain to each participant the nature of the study, its purpose, the procedures involved, the expected duration, the potential risks and benefits and any discomfort it may entail. Each participant will be informed that the participation in the study is voluntary and that he/she may withdraw from the study at any time and that withdrawal of consent will not affect his/her subsequent medical assistance and treatment.

All participants for the study will be provided with a participant information sheet,a consent form describing the study and providing sufficient information for participant to make an informed decision about their participation in the study and a prepaid envelope. Each patient may decide separately to participate in a) longitudinal follow-up questionnaires, b) blood tests or c) both parts of the study (questionnaire and blood samples). The delay for reflection will be 24 h. Once this period has expired, if the patient agrees to participate in the study, he or she is asked to return the consent form in the prepaid envelope. If he or she has not been send back after one week, the physician will call the patient by phone to make sure that it is not an omission.

The patient information sheet and the consent form are submitted to the Ethic comitee to be reviewed and approved. The formal consent of a participant, using the approved consent form, must be obtained before the participant is submitted to any study procedure.

The participant should read and consider the statement before signing and dating the informed consent form, and should be given a copy of the signed document. If the patient sent back the informed consent, a next appointment will be scheduled at the CRR where he or she will be asked to submit the signed consent form. The consent form must also be signed and dated by the investigator (or his designee) and it will be retained as part of the study records.

The total duration of the project is planned over a six years period (2019-2024). The study will be proposed to every CRPS ambulatory patient in the CRR (2019-2022), inclusion period). The study will also be proposed to the patients during the last two years (2023-2024) but only partially, since that last questionnaires will be sent in December 2024.

The CRPS patients are monitored on a regular and long-term basis at the CRR. The physician see them very regularly at the beginning (about once a month) and then the visits space a little out. Thus, our study fits into routine procedure and should not imply additional visits.

At the first visit at the clinic, the physician will proposed the study to the patient. Upon acceptance, the patient will be included into the study. It consists in five measurement times:

* T0: During the days following the first visit to the clinic
* T1: Follow up visit 3 months later
* T2: Follow up visit 6 months later
* T3: Follow up visit 12 months later
* T4: Follow up visit 24 months later

Conditions

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Complex Regional Pain Syndrome Type I

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients with CRPS type 1: prospective group

Ambulatory patients of the Clinique romande de réadaptation (CRR) which have a CRPS type 1 of a limb.

Five measurement times (first visit (T0) and then after 3 (T1), 6 (T2), 12 (T3) and 24 (T4) months). At every time point, following data will be collected: physical examination, monitoring of the health and professional status with the physician, and self-administrated questionnaires. Blood sampling will be performed at T0, T1,T2 and T3.

Eight different self-administrated questionnaires will be used, in their French or Portuguese version. Each participants will answer seven questionnaires each time, depending if he/she suffers of arm or leg injury.

We will assess, in blood samples, the expression levels of specific molecules (miRNAs and a selection of cytokines) in patients diagnosed with acute CRPS. In a second time, miRNAs and cytokines profiles will be compared between acute and chronic (CRPS still diagnosed 6 months after the first diagnosis) CRPS patients.

Administration of questionnaires for prospective group

Intervention Type OTHER

Questionnaires: administration at T0, T1,T2,T3 and T4 of Short Form Health Survey (SF-36),Brief Pain Inventory (BPI),Disabilities of the Arm, Shoulder and Hand (DASH) for upper limb,Foot and Ankle Ability Measure (FAAM) for lower limb,Hospital Anxiety And Depression Scale (HADS),Tampa Scale of Kinesiophobia (TSK),Pain Catastrophizing Scale (PCS),Pattern Of Activity Measure - Pain (POAM-P) .

Blood samples for prospective group

Intervention Type OTHER

Blood samples at T0,T1,T2 and T3.

control group for blood analysis

For the blood analysis, we will recruit 30 healthy controls who did not report any kind of pain. They will be recruited via posters that will be posted on the billboards of the Hôpital de Sion (employees and visitors) and on the visitor's billboards of the CRR. If this is not enough, we will expand the recruitment perimeter with other locations. The healthy control will be adjusted for age, sex and BMI with the CRPS groups. They will be informed about the study and procedure. The procedure for the blood samples will be the same as for patients.The screening for miRNAs of interest will be performed using a decision tree-based ensemble method (Random Forest). For this step, miRNAs profile of 30 control patients will be compared to the same number of CRPS patients.

The control group will have just one blood analysis.

Blood samples for control group

Intervention Type OTHER

Blood samples just one time

Interventions

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Administration of questionnaires for prospective group

Questionnaires: administration at T0, T1,T2,T3 and T4 of Short Form Health Survey (SF-36),Brief Pain Inventory (BPI),Disabilities of the Arm, Shoulder and Hand (DASH) for upper limb,Foot and Ankle Ability Measure (FAAM) for lower limb,Hospital Anxiety And Depression Scale (HADS),Tampa Scale of Kinesiophobia (TSK),Pain Catastrophizing Scale (PCS),Pattern Of Activity Measure - Pain (POAM-P) .

Intervention Type OTHER

Blood samples for prospective group

Blood samples at T0,T1,T2 and T3.

Intervention Type OTHER

Blood samples for control group

Blood samples just one time

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* CRPS Type I (fulfilling Budapest criteria for research)
* Suffering of CRPS in a distal limb (hand or foot)
* Age \>18 years
* Pain lasting less than 6 months
* Good understanding of the French language


* Not suffering from chronic pain, including CRPS
* Age \>18 years

Exclusion Criteria

* Known or suspected non-compliance, drug or alcohol abuse,
* Inability to follow the procedures of the study, e.g. due to language problems, severe psychological disorders, dementia, etc
* For blood sample: diabetes and history of hepatitis B, C, D or HIV infection
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Clinique Romande de Readaptation

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bertrand Léger, PhD

Role: STUDY_DIRECTOR

institut de recherche en réadaptatation

Locations

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Clinique romande de réadaptation

Sion, Valais, Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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michel Konzelmann, MD

Role: CONTACT

+41 79 314 84 84

Facility Contacts

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michel konzelmann, MD

Role: primary

+41 79 314 84 84

References

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Konig S, Schlereth T, Birklein F. Molecular signature of complex regional pain syndrome (CRPS) and its analysis. Expert Rev Proteomics. 2017 Oct;14(10):857-867. doi: 10.1080/14789450.2017.1366859. Epub 2017 Aug 17.

Reference Type BACKGROUND
PMID: 28803495 (View on PubMed)

Harden NR, Bruehl S, Perez RSGM, Birklein F, Marinus J, Maihofner C, Lubenow T, Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Chont M, Vatine JJ. Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome. Pain. 2010 Aug;150(2):268-274. doi: 10.1016/j.pain.2010.04.030. Epub 2010 May 20.

Reference Type BACKGROUND
PMID: 20493633 (View on PubMed)

Orlova IA, Alexander GM, Qureshi RA, Sacan A, Graziano A, Barrett JE, Schwartzman RJ, Ajit SK. MicroRNA modulation in complex regional pain syndrome. J Transl Med. 2011 Nov 10;9:195. doi: 10.1186/1479-5876-9-195.

Reference Type BACKGROUND
PMID: 22074333 (View on PubMed)

Galer BS, Henderson J, Perander J, Jensen MP. Course of symptoms and quality of life measurement in Complex Regional Pain Syndrome: a pilot survey. J Pain Symptom Manage. 2000 Oct;20(4):286-92. doi: 10.1016/s0885-3924(00)00183-4.

Reference Type BACKGROUND
PMID: 11027911 (View on PubMed)

Bean DJ, Johnson MH, Heiss-Dunlop W, Kydd RR. Extent of recovery in the first 12 months of complex regional pain syndrome type-1: A prospective study. Eur J Pain. 2016 Jul;20(6):884-94. doi: 10.1002/ejp.813. Epub 2015 Nov 2.

Reference Type BACKGROUND
PMID: 26524108 (View on PubMed)

Bean DJ, Johnson MH, Heiss-Dunlop W, Kydd RR. Factors Associated With Disability and Sick Leave in Early Complex Regional Pain Syndrome Type-1. Clin J Pain. 2016 Feb;32(2):130-8. doi: 10.1097/AJP.0000000000000234.

Reference Type BACKGROUND
PMID: 25803756 (View on PubMed)

Bean DJ, Johnson MH, Heiss-Dunlop W, Lee AC, Kydd RR. Do psychological factors influence recovery from complex regional pain syndrome type 1? A prospective study. Pain. 2015 Nov;156(11):2310-2318. doi: 10.1097/j.pain.0000000000000282.

Reference Type BACKGROUND
PMID: 26133727 (View on PubMed)

Birklein F, Ajit SK, Goebel A, Perez RSGM, Sommer C. Complex regional pain syndrome - phenotypic characteristics and potential biomarkers. Nat Rev Neurol. 2018 May;14(5):272-284. doi: 10.1038/nrneurol.2018.20. Epub 2018 Mar 16.

Reference Type BACKGROUND
PMID: 29545626 (View on PubMed)

Le Carre J, Lamon S, Leger B. Validation of a multiplex reverse transcription and pre-amplification method using TaqMan((R)) MicroRNA assays. Front Genet. 2014 Nov 26;5:413. doi: 10.3389/fgene.2014.00413. eCollection 2014.

Reference Type BACKGROUND
PMID: 25505484 (View on PubMed)

Other Identifiers

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CliniqueRR-20

Identifier Type: -

Identifier Source: org_study_id

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