Ignite Creation Date:
2024-05-06 @ 3:32 PM
Last Modification Date:
2024-10-26 @ 1:51 PM
Study NCT ID:
NCT04667364
Status:
TERMINATED
Last Update Posted:
2023-04-24
First Post:
2020-11-30
Brief Title:
Pain in Complex Regional Pain Syndrome
Sponsor:
Hospital of South West Jutland
Organization:
Hospital of South West Jutland
Study Overview
Official Title:
Modulation of Pain Sensitization in Complex Regional Pain Syndrome
Status:
TERMINATED
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of recruitment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
CRPS is a complex pain condition that usually develops in response to trauma and immobilization which is very painful and debilitating There is no consensus about the underlying mechanisms which might be a combination of mentally and physically factors At the moment better diagnostic clarification and better pain relieving treatment is needed The aim of this study is to investigate changes in the perception of pain in patients with Complex Regional Pain Syndrome CRPS and whether this perception can be affected by treatment with transcutaneous electrical nerve stimulation TENS on the painful area The study will consist of two parts One in which patients perception of pain will be compared to the perception of pain in healthy controls Another in which the included patients are randomly allocated into a group receiving medical treatment plus treatment with transcutaneous electrical nerve stimulation on the painful area or in a group receiving medical treatment as usual MEDPatients will be evaluated four times At the start of the study immediately after treatment and again at 6 and 12 months after treatment The evaluation consists of an overall assessment of pain response to standardized sensory stimuli and questionnaires about quality of life physical capacity and mentallysocially well-being
Detailed Description:
BACKGROUND Chronic pain represents a major challenge worldwide with significant clinical social and economic implications Complex regional pain syndrome CRPS is a chronic pain condition that usually but not exclusively develops in response to acute trauma or surgery It is characterized by pain disproportionate to the preceding trauma in addition to sensory abnormalities and autonomic disturbances trophic changes and impaired motor function Reports indicate that the incidence of CRPS is 262100000 life-years with a 351 female male ratio and with a mean age at diagnosis 527y The condition is complex and is probably the result of multimodal pathogenesis that has a significant impact on daily functioning and quality of life QoL In addition few cases resolve completely within 12 months of onset has a large impact on work ability and some develop chronic pain and disability The socioeconomic consequences are therefore substantial and an increased focus on CRPS diagnosis and treatment is needed Because of the complexity of the condition treatment is difficult and include physiotherapy education spinal cord stimulation SCS and medical treatment Primary treatment involves medical treatment which might include important adverse effects such as fatigue insomnia anxiety and weight gain to name a few Regardless results vary significantly One explanation is the multimodality of pain that involves both peripheral nerves the spinal cord and higher brain centers modulated by immune cells interneurons descending pathways cognitive and psychosocial factors Changes in pain sensitization has been proposed to be a driving factor in CRPS and is the result of distorted somatosensory signaling in the central nervous system Pain normally reflects damaging peripheral input acting as an important protective function however this concept might get distorted so that pain no longer represent peripheral noxious stimuli but rather functional changes of the central nervous system The pain in these situations arises spontaneously can be elicited by normally innocuous stimuli allodynia is exaggerated and prolonged in response to noxious stimuli hyperalgesia and spreads beyond the site of injury secondary hyperalgesia Testing some of the underlying mechanisms provides the means to directly evaluate these pain symptoms suggested to be among the primary complaints in CPRS Accordingly a range of sensory changes has been suggested including thermal and mechanical hyperalgesia and hypoesthesia A study found hyperalgesia to blunt pressure in patients with CRPS and with peripheral nerve injury which has been confirmed by others suggesting an importance of deep somatic structures such as muscles and bones Another study showed changes in thermal sensitivity with both heat and cold hyperalgesia in the acute phase of CRPS and a modulation of thermal detection thresholds as the CRPS progressed In addition a study reported changes in endogenous pain modulation implying a shift towards facilitation whereas others found limited change These differential results alongside heterogeneous mechanisms associated with diverse clinical features complicates treatment significantly which might only affect a small portion of patients It is crucial to establish whether patients can be identified and distinguished to facilitate optimal decisions and effects of treatment strategies This project applies a psychophysical method based on conventional quantitative sensory testing QST to quantify somatosensory function in CRPS patients to provide a mechanisms-based approach to diagnosis and treatment Recently QST has been used to complement traditional neurological testing with greater precision and reliability when assessing somatosensory aberrations and its clinical value is well recognized Nevertheless because of a lack of standardization and a paucity in normative data the application of QST in clinical settings remains scarce The current project applies QST methodology developed at the Spine center of Southern Denmark Lillebaelt Hospital specifically designed to meet clinical demands and will be part of a novel initiative to implement and standardize QST in clinical practice in Denmark The methodology might prove valuable in a range of different pathologies such as headache fibromyalgia and diabetic neuropathy In addition the current project will combine QST measurement with functional measurements and patient reported outcomes on depression anxiety and sleep using a national database on pain in collaboration with Pain Center South University Hospital Odense The modulation of QST their interaction and time course together with functional measurements and PRO-data might be a powerful combination for the diagnosis of patients monitoring and prediction of therapy success A therapy often used as an adjunct to medication is transcutaneous electrical nerve stimulation TENS which is an inexpensive noninvasive and safe treatment for pain Electrical stimulation is delivered to peripheral sensory nerves using surface electrodes and has been shown to have a beneficial effect on centralized pain showing normalized hyperalgesia post intervention Nevertheless the beneficial effects remain controversial as more high-quality studies are needed In addition pain is complex and depends on contextual social psychological and biological factors not necessarily attributed to a specific pathology These are rarely considered concurrently The current project will evaluate the effect of TENS in respect to patients psychological functional and somatosensory profile adding valuable information to the existing body of literature
The aim of the current project is three-fold 1 to test the feasibility and validity of standardized quantitative sensory testing for CRPS in clinical practice 2 to evaluate changes in sensitization and 3 to evaluate the effectiveness of transcutaneous electrical nerve stimulation TENS and identify subgroups that benefit the most
The investigators hypothesize that quantitative sensory testing is feasible in a clinical setting and will in combination with functional measurements and PRO-data be a valuable tool for the diagnosis of patients and for the monitoring and prediction of therapy success
TRIAL DESIGN The project will utilize quantitative methods and strong randomized controlled research designs The project will consist of two parts 1 Evaluation of CRPS patient compared to healthy controls and validation of method Participants will be assessed at baseline prior to treatment with QST mechanical stimulation pain thresholds coldheat sensitivity as outcome measure to identify somatosensory profiles of CRPS patients compared to normative data 2 Evaluation of treatment with TENS compared to treatment as usual Patients will be randomly allocated to either a TENS intervention group TENS or a treatment as usual group MED and will be assessed at baseline re-test pre TENS post intervention and 3 month post intervention Outcomes include QST and patient reported outcomes pain quality of life depression anxiety sleep am Subsequent analysis of data is planned to evaluate its ability to predict therapeutic outcomes of TENS
RECRUITMENT AND SAMPLE SIZE Patients will be recruited from the clinic for CRPS and neuropathic pain Hospital of South West Jutland SVS University Hospital of Southern Denmark The clinic functions as a specialized CRPS clinic in the Region of Southern Denmark Healthy controls will be recruited amongst staff at SVS and partners relatives or friends
The planned number of trial participants is based on the assumed superiority of TENS treatment over control Estimating the sample size for a two-sample means test with a level of significance at 005 assuming a common standard deviation SD of 2 in NRS pain intensity scores indicates that for the intention-to-treat ITT population 34 individuals is required to obtain a power of at least 80 to establish a minimal clinically significant difference MCSD of 2 in NRS pain scores The MCSD and common standard deviation is based on previous findings with a similar patient group and intervention With an expected drop-out rate of 20 a total of 46 individuals will be included in the project 23 in each group
ALLOCATION All patients will be evaluated at baseline and their QST data will be compared to a group of healthy controls Part 1 Subsequently in part 2 patients will be randomized with a computer-generated block randomization with a 11 allocation ratio using random block sizes of 2 4 and 6 in either group TENS or group MED The randomization restrictions will not be disclosed and the sequence will be performed by an external party
INTERVENTIONS TENS Conventional TENS will be performed using two electrodes placed on the involved extremity and with the following stimulation parameters a frequency of 100 Hz pulse duration 50-100 ms and at an intensity gradually increased until the patient feels a strong tolerable and non-painful sensation The intensity is incrementally increased based on patient feedback Patients will receive guidelines on how to use the TENS device at home and will over a period of 30 days self-administer TENS as needed Patients is to fill out a predefined schedule on paper each day to monitor dose see appendix
Treatment as usual Consist of medicinal treatment prescribed by a specialist doctor Carsten Kock-Jensen MD from the CRPS clinic and will be monitored using patients medicinal records
STATISTICAL METHODS To evaluate the empirical distributions of the continuous outcomes visual inspection of the studentized residuals will be applied to evaluate whether the assumption of normality is reasonable The treatment groups will be examined for comparability based on baseline demographic and prognostic measures An Intention-To-Treat ITT analysis will be used for all allocated patients and a mixed effects model will be used on the continuous outcome measures to determine the effects of TENS treatment from baseline to post treatment and follow-ups Between groups factor TENS vs MED within groups factor time The model will use robust estimation methods to account for outliers Finally a multiple imputation approach will be used in case of missing data All p-values 005 will be considered statistically significant
ETHICS AND SIGNIFICANCE The project is to be approved by the Regional Committee on Health Research Ethics for Southern Denmark and will be conducted according to the declaration of Helsinki
The combination of quantitative pain measurements and PRO-data might be a powerful combination for the diagnosis of patients and monitoring and prediction of therapy success It might have the potential to provide patients with individualized mechanism-based pain therapy and clarify to what extend and to whom TENS is beneficial This might result in increased functional capacity and quality of life as a result of significant pain relief This could have a significant impact on patients lives as well as significant socioeconomic consequences
The aim of the current project is three-fold 1 to test the feasibility and validity of standardized quantitative sensory testing for CRPS in clinical practice 2 to evaluate changes in sensitization and 3 to evaluate the effectiveness of transcutaneous electrical nerve stimulation TENS and identify subgroups that benefit the most
The investigators hypothesize that quantitative sensory testing is feasible in a clinical setting and will in combination with functional measurements and PRO-data be a valuable tool for the diagnosis of patients and for the monitoring and prediction of therapy success
TRIAL DESIGN The project will utilize quantitative methods and strong randomized controlled research designs The project will consist of two parts 1 Evaluation of CRPS patient compared to healthy controls and validation of method Participants will be assessed at baseline prior to treatment with QST mechanical stimulation pain thresholds coldheat sensitivity as outcome measure to identify somatosensory profiles of CRPS patients compared to normative data 2 Evaluation of treatment with TENS compared to treatment as usual Patients will be randomly allocated to either a TENS intervention group TENS or a treatment as usual group MED and will be assessed at baseline re-test pre TENS post intervention and 3 month post intervention Outcomes include QST and patient reported outcomes pain quality of life depression anxiety sleep am Subsequent analysis of data is planned to evaluate its ability to predict therapeutic outcomes of TENS
RECRUITMENT AND SAMPLE SIZE Patients will be recruited from the clinic for CRPS and neuropathic pain Hospital of South West Jutland SVS University Hospital of Southern Denmark The clinic functions as a specialized CRPS clinic in the Region of Southern Denmark Healthy controls will be recruited amongst staff at SVS and partners relatives or friends
The planned number of trial participants is based on the assumed superiority of TENS treatment over control Estimating the sample size for a two-sample means test with a level of significance at 005 assuming a common standard deviation SD of 2 in NRS pain intensity scores indicates that for the intention-to-treat ITT population 34 individuals is required to obtain a power of at least 80 to establish a minimal clinically significant difference MCSD of 2 in NRS pain scores The MCSD and common standard deviation is based on previous findings with a similar patient group and intervention With an expected drop-out rate of 20 a total of 46 individuals will be included in the project 23 in each group
ALLOCATION All patients will be evaluated at baseline and their QST data will be compared to a group of healthy controls Part 1 Subsequently in part 2 patients will be randomized with a computer-generated block randomization with a 11 allocation ratio using random block sizes of 2 4 and 6 in either group TENS or group MED The randomization restrictions will not be disclosed and the sequence will be performed by an external party
INTERVENTIONS TENS Conventional TENS will be performed using two electrodes placed on the involved extremity and with the following stimulation parameters a frequency of 100 Hz pulse duration 50-100 ms and at an intensity gradually increased until the patient feels a strong tolerable and non-painful sensation The intensity is incrementally increased based on patient feedback Patients will receive guidelines on how to use the TENS device at home and will over a period of 30 days self-administer TENS as needed Patients is to fill out a predefined schedule on paper each day to monitor dose see appendix
Treatment as usual Consist of medicinal treatment prescribed by a specialist doctor Carsten Kock-Jensen MD from the CRPS clinic and will be monitored using patients medicinal records
STATISTICAL METHODS To evaluate the empirical distributions of the continuous outcomes visual inspection of the studentized residuals will be applied to evaluate whether the assumption of normality is reasonable The treatment groups will be examined for comparability based on baseline demographic and prognostic measures An Intention-To-Treat ITT analysis will be used for all allocated patients and a mixed effects model will be used on the continuous outcome measures to determine the effects of TENS treatment from baseline to post treatment and follow-ups Between groups factor TENS vs MED within groups factor time The model will use robust estimation methods to account for outliers Finally a multiple imputation approach will be used in case of missing data All p-values 005 will be considered statistically significant
ETHICS AND SIGNIFICANCE The project is to be approved by the Regional Committee on Health Research Ethics for Southern Denmark and will be conducted according to the declaration of Helsinki
The combination of quantitative pain measurements and PRO-data might be a powerful combination for the diagnosis of patients and monitoring and prediction of therapy success It might have the potential to provide patients with individualized mechanism-based pain therapy and clarify to what extend and to whom TENS is beneficial This might result in increased functional capacity and quality of life as a result of significant pain relief This could have a significant impact on patients lives as well as significant socioeconomic consequences
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None