Near-infrared Spectroscopic Measurement in Complex Regional Pain Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Geoff Bellingham, Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT01586377
First received: April 24, 2012
Last updated: July 2, 2013
Last verified: July 2013
  Purpose

Recent clinical investigations have suggested that the cause of abnormal pain in complex regional pain syndrome could be ischemia and inflammation, due to poor blood flow to deep tissues from microvascular pathology. This study aims to determine if a new technology called near infrared spectroscopy can measure this microvascular dysfunction. The study hypothesizes that significant differences can be measured in the microcirculation of patients with CRPS-I using near infrared spectroscopy and the vascular occlusion test.


Condition
Reflex Sympathetic Dystrophy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Near-infrared Spectroscopic Measurement of Tissue Oxygen Saturation and the Vascular Occlusion Test in Complex Regional Pain Syndrome

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:
  • Baseline tissue oxygen saturation [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Occlusion slope during vascular occlusion test [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Reperfusion slope during vascular occlusion test [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Delta StO2 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Defined as the difference between the maximal tissue oxygenation value after reperfusion and the baseline measurement

  • Post-obstructive hyperemic response [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Thenar muscle oxygen consumption [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: August 2011
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
CRPS Type 1
Patients with CRPS 1 affecting a single upper limb
Healthy volunteers
Volunteers without the diagnosis of CRPS Type 1

Detailed Description:

The pathophysiology of CRPS-1 is unknown yet a considerable number of studies suggest that the fundamental cause of abnormal pain is due to microvascular pathology of deep tissues.

Reduced blood flow to deep tissues such as muscle, nerve, and bone can lead to a combination of inflammatory and neuropathic pain processes (Coderre TJ et al. 2010). Evidence to support this model of microcirculatory dysfunction includes observations that skin capillary oxygenation is decreased and skin lactate is increased in affected limbs of patients (total of 11 patients in lactate study) (Birklein F et al. 2000, Manahan AP et al. 2007). It has also been reported that patients with CRPS-I have abnormal vasodilatory responses after sympathetically-mediated vasoconstriction (Dayan L et al. 2008) and decreased concentrations of nitric oxide in the affected limb (Groeneweg JG et al. 2006).

Near-infrared spectroscopy (NIRS) is a non-invasive method of measuring tissue oxygenation using the differential absorption properties of oxygenated and deoxygenated hemoglobin in biological tissue (Creteur J 2008). Near-infrared light is only transmitted through small vessels with diameter less than 1 mm (arterioles, venules and capillaries). Since NIRS is limited to monitoring only small vessels, it can be used to assess oxygen balance in the microcirculation of skeletal muscle (Creteur J 2008).

Premises Premise 1: Complex regional pain syndrome is associated with microcirculatory dysfunction

After an injury to a patient's limb, it is hypothesized that the pressure exerted by that swelling within a relatively confined anatomical space can occlude the capillaries of adjacent tissues and cause a compartment syndrome-like injury. Coderre et al. (2010) have theorized that the resulting microcirculatory dysfunction causes a persistent inflammatory state which is then responsible for pain generation.

In an animal model of ischemia-reperfusion injury used to study CRPS-1, microscopy of muscle and nerve tissue demonstrates microvascular evidence of a slow-flow/no-reflow phenomenon (Coderre TJ et al. 2010). Existence of a slow-flow/no-reflow state causes persistent inflammation in deep tissue. Animals subsequently develop hyperemia and edema, followed by mechano-hyperalgesia, allodynia, and cold-allodynia lasting for at least 1 month (Coderre et al. 2010). This clinical picture is similar to the clinical signs of those patients afflicted with CRPS-1.

Premise 2: Vascular occlusion testing measures microcirculatory dysfunction NIRS measurement of peripheral tissue oxygen saturation (StO2), combined with a reproducible ischemia-reperfusion challenge to induce reactive hyperemia (vascular occlusion testing - VOT), has been described as a valid and reliable method for assessing microcirculatory dysfunction (De Backer et al. 2010). This involves a short period of forearm ischemia by inflating a blood pressure cuff on the upper arm. The blood pressure cuff is then released after approximately 3 minutes and this followed by reperfusion of the forearm. This stimulates the release of endogenous nitric oxide (NO) from the microvascular endothelium (Harel et al 2008). Measurement of this hyperemic response using NIRS has been demonstrated to be a feasible non-invasive method of quantifying microcirculatory function. This technique shares strong correlation with the gold-standard method of strain gauge plethysmography (Harel et al. 2008).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients with CRPS Type 1 will be selected from a tertiary care chronic pain clinic. Healthy volunteers will be selected from a community sample

Criteria

Inclusion Criteria:

  • Complex regional pain syndrome type 1 (CRPS-I) of one upper extremity.
  • Healthy volunteers.
  • Diagnosis of CRPS-I established for greater than 12 weeks.

Exclusion Criteria:

  • Pregnancy
  • Lack of informed consent
  • History of peripheral vascular disease requiring angioplasty or bypass surgery
  • History of systemic vasculitis
  • Current use of vasoactive medications
  • Diabetes Type I and II
  • Presently smoking
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01586377

Locations
Canada, Ontario
Pain Clinic, St. Joseph's Health Care London Hospitals
London, Ontario, Canada, N6A 4V2
Sponsors and Collaborators
Lawson Health Research Institute
Investigators
Principal Investigator: Geoff A Bellingham, MD FRCPC University of Western Ontario, Canada
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Geoff Bellingham, Principal Investigator, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT01586377     History of Changes
Other Study ID Numbers: R-11-382, 18119
Study First Received: April 24, 2012
Last Updated: July 2, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Lawson Health Research Institute:
Complex regional pain syndrome
Near Infrared Spectroscopy
Vascular Occlusion Test

Additional relevant MeSH terms:
Reflex Sympathetic Dystrophy
Complex Regional Pain Syndromes
Autonomic Nervous System Diseases
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on August 19, 2014