Clinical trial NCT01813149: Mechanism and Treatment of Sympathetically Maintained Pain
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Complex Regional Pain Syndrome (CRPS)
Keywords: Complex Regional Pain Syndrome (CRPS)
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Murdoch University
First posted: 2013-03-18
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is best thought of as a single-arm study because the primary purpose for recruiting control patients is to use their skin biopsies as controls when running immunohistochemistry tests for determining α1-adrenoceptors (α1-AR) expression in CRPS patients. The primary outcomes are concerned with making comparisons between subgroups of CRPS patients, and not between CRPS patients and control patients.
Primary purpose: BASIC_SCIENCE

Brief summary: 40 CRPS patients will be recruited over a three-year period (target of 160 patients at all sites). Assessment of exclusion criteria will be undertaken during initial recruitment. Exclusion criteria are: \<18 years; a second chronic pain syndrome that would interfere with pain rating; psychiatric comorbidity; pain in both hands or feet; pregnancy or breastfeeding; sympathectomy in the affected limb; use of topical medication; known sensitivity to alpha 1- adrenoceptor agonists or other contraindications. Patients will maintain their regular oral medications throughout the study period.

Assessment of sympathetically maintained pain (SMP) will require an intradermal dose of Phenylephrine to rekindle SMP and mechanical hyperalgesia. Clonidine will be used to control for affects of algometer fiction and may inhibit SMP by inhibiting the release of more norepinephrine from sympathetic nerve terminals. Skin biopsies will be obtained under sterile conditions from a site of mechanical or thermal hyperalgesia using a 3mm diameter skin biopsy punch under local anesthesia. Samples from a mirror image site on the contralateral body side will also be taken.

Detailed description: Patients diagnosed with CRPS and control subjects will be enrolled in the study. The CRPS participants will be administered with phenylephrine (day 1) and clonidine (day 2). The control participants will not receive any intervention.

The aim of this study is to determine if expression of α1-adrenoceptors (α1-AR) altered in the skin of a subgroup of patients whose pain is associated with increased adrenergic sensitivity after nerve trauma. Increased adrenergic sensitivity will be determined by assessing pain in patients after administration of phenylephrine on day 1. Expression of α1-AR will be determined by taking skin biopsies on day 2 after administration of clonidine. Then, we will compare the expression of α1-AR in patients who were classified as having increased adrenergic sensitivity versus those who were not.

Eligibility criteria: Inclusion Criteria:

* CRPS patients

Exclusion Criteria:

* \<18 years
* a second chronic pain syndrome that would interfere with pain rating
* psychiatric comorbidity
* pain in both hands or feet
* pregnancy or breastfeeding
* sympathectomy in the affected limb
* use of topical medication
* known sensitivity to alpha 1- adrenoceptor agonists or other contraindications

Primary outcomes:
measure: Increased Adrenergic Sensitivity
timeFrame: Day 1
measure: Expression of α1-adrenoceptors (α1-AR) in Dermal Nerve Bundles in the CRPS-affected Limb of Phenylephrine Responders and Non-responders
timeFrame: Day 2, after clonidine injection
measure: Expression of Pain Association With Chronic Inflammation in Patients With Sympathetically Maintained Pain
timeFrame: Day 1
measure: Decrease in Pain After Topical Adrenoceptor Blockade
timeFrame: 2 weeks after blockade
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
References: