Mechanism and Treatment of Sympathetically Maintained Pain

NCT01813149 | Terminated Results

• 1 other identifier: 12-400
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

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.

Conditions

Complex Regional Pain Syndrome (CRPS)

Keywords

Complex Regional Pain Syndrome (CRPS)

Outcome Measures

Primary Outcomes (4)

• Increased Adrenergic Sensitivity

  To investigate adrenergically evoked pain, 50 mg of the a1-AR agonist phenylephrine in 0.1 mL normal saline (equivalent to 2.5mMconcentration was injected intradermally into the most painful region of the dorsal and or foot and into a mirror-image site in the contralateral limb. Pain induced by the intradermal injection of phenylephrine into the contralateral limb of patients with CRPS usually resolved within 5 to 10 minutes. Therefore, pain that persisted for 15 minutes or longer (in the CRPS-affected limb) was considered to be atypical. Using this criterion, subjects who reported prolonged pain (a sign of adrenergic sensitivity) following the phenylephrine injection were classified as phenylephrine responders and those who didn't were classified as phenylephrine non-responders.

  Day 1

• Expression of α1-adrenoceptors (α1-AR) in Dermal Nerve Bundles in the CRPS-affected Limb of Phenylephrine Responders and Non-responders

  Expression of α1-AR was determined from the skin biopsies using immunohistochemistry. Nerve bundles in the reticular dermis were identified in the affected limb of 25 patients with CRPS \[only 22 of these were classified as phenylephrine responders/non-responders\], in the contralateral limb of 21 patients with CRPS, and in 12 controls. Samples were processed in batches containing sections from 10 controls and from the affected and contralateral limbs of 10 patients. The α1-AR immunoreactivity (a measure of the expression of receptors) scores were transformed into standard units with a mean of 0 and a SD of 1 (ie, Z-scores). Positive scores represent greater than average α1-AR immunoreactivity (i.e. higher expression of α1-AR) compared with other samples in the run, and negative scores represent less than average α1-AR immunoreactivity. Normalized scores were averaged across multiple runs for each patient or control to obtain a mean α1-AR score.

  Day 2, after clonidine injection

• Expression of Pain Association With Chronic Inflammation in Patients With Sympathetically Maintained Pain

  Determine whether heightened expression of cutaneous 1-adrenoceptors is associated with signs of chronic inflammation in patients with sympathetically maintained pain

  Day 1

• Decrease in Pain After Topical Adrenoceptor Blockade

  2 weeks after blockade

Study Arms (1)

phenylephrine and clonidine

EXPERIMENTAL

Subjects will be injected with phenylephrine and clonidine at affected and unaffected sites.

Drug: phenylephrine and clonidine; Other: punch biopsy

Interventions

phenylephrine and clonidine DRUG

Subjects will be injected with phenylephrine and clonidine at both affected and unaffected sites.

phenylephrine and clonidine

punch biopsy OTHER

Also known as: After local anesthetic, subjects will receive punch biopsy (1/8"diameter and 1/8" deep) from both affected and unaffected sites.

phenylephrine and clonidine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CRPS patients

You may not qualify if:

• \<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

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Murdoch University: collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Complex Regional Pain Syndromes

Interventions

Phenylephrine; Clonidine

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Michael Stanton Hicks, MD
• Organization: Cleveland Clinic Foundation

stantom@ccf.org

216-445-3497

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 12, 2013
• First Posted: March 18, 2013
• Study Start: August 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 13, 2021
• Results First Posted: January 13, 2021

Record last verified: 2020-12

Locations

US (1)