Reflex Sympathetic DystrophyNCT01586377
Near-infrared Spectroscopic Measurement in Complex Regional Pain Syndrome
An observational study of Reflex Sympathetic Dystrophy, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Reflex Sympathetic Dystrophy
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2011to Jul 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- Complex regional pain syndrome type 1 (CRPS-I) of one upper extremity.
- Healthy volunteers.
- Diagnosis of CRPS-I established for greater than 12 weeks.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Pain Clinic, St. Joseph's Health Care London Hospitals
London, Ontario, N6A 4V2
About this study
Official title: Near-infrared Spectroscopic Measurement of Tissue Oxygen Saturation and the Vascular Occlusion Test in Complex Regional Pain Syndrome
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.
Read the 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).
- Conditions
- Reflex Sympathetic Dystrophy
- Keywords
- Complex regional pain syndrome, Near Infrared Spectroscopy, Vascular Occlusion Test
- Medical subject headings
- Reflex Sympathetic Dystrophy, Complex Regional Pain Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CRPS Type 1 | Patients with CRPS 1 affecting a single upper limb | |
| Healthy volunteers | Volunteers without the diagnosis of CRPS Type 1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline tissue oxygen saturation
Measured: Day 1
Secondary outcomes (5)
Occlusion slope during vascular occlusion test
Measured: Day 1
Reperfusion slope during vascular occlusion test
Measured: Day 1
Delta StO2
Defined as the difference between the maximal tissue oxygenation value after reperfusion and the baseline measurement
Measured: Day 1
Post-obstructive hyperemic response
Measured: Day 1
Thenar muscle oxygen consumption
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2012 (estimated)
- Study startAug 2011
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Reflex Sympathetic DystrophyStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Geoff Bellingham, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Geoff A Bellingham, MD FRCPC, Principal investigator, Western University, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01586377
- Sponsor's protocol ID
- R-11-382
- Other IDs
- 18119
- Status last verified
- Jul 2013
- First submitted
- 24 Apr 2012
- Last updated
- 3 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Birklein F, Weber M, Neundorfer B. Increased skin lactate in complex regional pain syndrome: evidence for tissue hypoxia? Neurology. 2000 Oct 24;55(8):1213-5. doi: 10.1212/wnl.55.8.1213.
PubMed 11071503Creteur J. Muscle StO2 in critically ill patients. Curr Opin Crit Care. 2008 Jun;14(3):361-6. doi: 10.1097/MCC.0b013e3282fad4e1.
PubMed 18467900Coderre TJ, Bennett GJ. A hypothesis for the cause of complex regional pain syndrome-type I (reflex sympathetic dystrophy): pain due to deep-tissue microvascular pathology. Pain Med. 2010 Aug;11(8):1224-38. doi: 10.1111/j.1526-4637.2010.00911.x.
PubMed 20704671Dayan L, Salman S, Norman D, Vatine JJ, Calif E, Jacob G. Exaggerated vasoconstriction in complex regional pain syndrome-1 is associated with impaired resistance artery endothelial function and local vascular reflexes. J Rheumatol. 2008 Jul;35(7):1339-45. Epub 2008 May 1.
PubMed 18464300De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent JL. Monitoring the microcirculation in the critically ill patient: current methods and future approaches. Intensive Care Med. 2010 Nov;36(11):1813-25. doi: 10.1007/s00134-010-2005-3. Epub 2010 Aug 6.
PubMed 20689916Doerschug KC, Delsing AS, Schmidt GA, Haynes WG. Impairments in microvascular reactivity are related to organ failure in human sepsis. Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1065-71. doi: 10.1152/ajpheart.01237.2006. Epub 2007 May 4.
PubMed 17483235Groeneweg JG, Huygen FJ, Heijmans-Antonissen C, Niehof S, Zijlstra FJ. Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1. BMC Musculoskelet Disord. 2006 Nov 30;7:91. doi: 10.1186/1471-2474-7-91.
PubMed 17137491Harel F, Denault A, Ngo Q, Dupuis J, Khairy P. Near-infrared spectroscopy to monitor peripheral blood flow perfusion. J Clin Monit Comput. 2008 Feb;22(1):37-43. doi: 10.1007/s10877-007-9105-9. Epub 2007 Nov 27.
PubMed 18040873Skarda DE, Mulier KE, Myers DE, Taylor JH, Beilman GJ. Dynamic near-infrared spectroscopy measurements in patients with severe sepsis. Shock. 2007 Apr;27(4):348-53. doi: 10.1097/01.shk.0000239779.25775.e4.
PubMed 17414414Bellingham GA, Smith RS, Morley-Forster P, Murkin JM. Use of near infrared spectroscopy to detect impaired tissue oxygen saturation in patients with complex regional pain syndrome type 1. Can J Anaesth. 2014 Jun;61(6):563-70. doi: 10.1007/s12630-014-0140-y. Epub 2014 Mar 26.
PubMed 24668314
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Near-infrared Spectroscopic Measurement of Tissue Oxygen Saturation and the Vascular Occlusion Test in Complex Regional Pain Syndrome
- ClinicalTrials.gov ID
- NCT01586377
- Acronym / sponsor ID
- R-11-382
- Conditions
- Reflex Sympathetic Dystrophy
- Keywords
- Complex regional pain syndrome, Near Infrared Spectroscopy, Vascular Occlusion Test
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 26 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CRPS Type 1 | – | –Patients with CRPS 1 affecting a single upper limb |
| Healthy volunteers | – | –Volunteers without the diagnosis of CRPS Type 1 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (3 listed)
- Complex regional pain syndrome type 1 (CRPS-I) of one upper extremity.
- Healthy volunteers.
- Diagnosis of CRPS-I established for greater than 12 weeks.
Key exclusion criteria (7 listed)
- Pregnancy
- Lack of informed consent
- History of peripheral vascular disease requiring angioplasty or bypass surgery
- History of systemic vasculitis
- Current use of vasoactive medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Baseline tissue oxygen saturation
Time frame: Day 1
5 secondary outcomes
Occlusion slope during vascular occlusion test
Time frame: Day 1
Reperfusion slope during vascular occlusion test
Time frame: Day 1
Delta StO2
Time frame: Day 1
Post-obstructive hyperemic response
Time frame: Day 1
Thenar muscle oxygen consumption
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2013.
- Background: PubMed 11071503Birklein F, Weber M, Neundorfer B. Increased skin lactate in complex regional pain syndrome: evidence for tissue hypoxia? Neurology. 2000 Oct 24;55(8):1213-5. doi: 10.1212/wnl.55.8.1213.
- Background: PubMed 18467900Creteur J. Muscle StO2 in critically ill patients. Curr Opin Crit Care. 2008 Jun;14(3):361-6. doi: 10.1097/MCC.0b013e3282fad4e1.
- Background: PubMed 20704671Coderre TJ, Bennett GJ. A hypothesis for the cause of complex regional pain syndrome-type I (reflex sympathetic dystrophy): pain due to deep-tissue microvascular pathology. Pain Med. 2010 Aug;11(8):1224-38. doi: 10.1111/j.1526-4637.2010.00911.x.
- Background: PubMed 18464300Dayan L, Salman S, Norman D, Vatine JJ, Calif E, Jacob G. Exaggerated vasoconstriction in complex regional pain syndrome-1 is associated with impaired resistance artery endothelial function and local vascular reflexes. J Rheumatol. 2008 Jul;35(7):1339-45. Epub 2008 May 1.
- Background: PubMed 20689916De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent JL. Monitoring the microcirculation in the critically ill patient: current methods and future approaches. Intensive Care Med. 2010 Nov;36(11):1813-25. doi: 10.1007/s00134-010-2005-3. Epub 2010 Aug 6.
- Background: PubMed 17483235Doerschug KC, Delsing AS, Schmidt GA, Haynes WG. Impairments in microvascular reactivity are related to organ failure in human sepsis. Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1065-71. doi: 10.1152/ajpheart.01237.2006. Epub 2007 May 4.
- Background: PubMed 17137491Groeneweg JG, Huygen FJ, Heijmans-Antonissen C, Niehof S, Zijlstra FJ. Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1. BMC Musculoskelet Disord. 2006 Nov 30;7:91. doi: 10.1186/1471-2474-7-91.
- Background: PubMed 18040873Harel F, Denault A, Ngo Q, Dupuis J, Khairy P. Near-infrared spectroscopy to monitor peripheral blood flow perfusion. J Clin Monit Comput. 2008 Feb;22(1):37-43. doi: 10.1007/s10877-007-9105-9. Epub 2007 Nov 27.
- Background: PubMed 17414414Skarda DE, Mulier KE, Myers DE, Taylor JH, Beilman GJ. Dynamic near-infrared spectroscopy measurements in patients with severe sepsis. Shock. 2007 Apr;27(4):348-53. doi: 10.1097/01.shk.0000239779.25775.e4.
- Derived from this study: PubMed 24668314Bellingham GA, Smith RS, Morley-Forster P, Murkin JM. Use of near infrared spectroscopy to detect impaired tissue oxygen saturation in patients with complex regional pain syndrome type 1. Can J Anaesth. 2014 Jun;61(6):563-70. doi: 10.1007/s12630-014-0140-y. Epub 2014 Mar 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geoff A Bellingham, MD FRCPC principal investigator
Western University, Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Reflex Sympathetic Dystrophy, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline tissue oxygen saturation (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01586377, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2013.