Imaging Pain Relief in Osteoarthritis (IPRO)
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|ClinicalTrials.gov Identifier: NCT02208778|
Recruitment Status : Completed
First Posted : August 5, 2014
Last Update Posted : November 27, 2017
Osteoarthritis (OA) is a degenerative joint disease and is the most common form of arthritis. Pain reduction and functional recovery are the key elements of the clinical management of OA. Current treatment guidelines recommend a combination of pharmacological and non-pharmacological treatments. However, these are not always effective, with nearly 20% of patients not responding to any standard therapy, including joint replacement.
The mechanisms of pain relief are not well understood and are complicated by the remarkably large placebo effect, and inter-individual variation. There is no objective criteria for predicting whether a patient will respond to a given treatment
Duloxetine, an antidepressant drug, has proven effectiveness in various chronic pain syndromes including knee OA. The effect is however limited and only clinically relevant in around half of the trial patients. Importantly, it is currently unclear how and in whom duloxetine alleviates chronic pain.
Advanced MRI techniques use strong magnetic fields and radio frequency signals to generate metabolic, anatomical and functional brain images (fMRI).
Remifentanil is a potent analgesic agent whose analgesic effect has been well characterised in healthy volunteers, including fMRI studies showing modulation of activation of regions in the brain related to pain processing. Nevertheless, the neural correlates of remifentanil effects have not yet been investigated in chronic pain patients.
The aim of this research is to use a combination of multimodal MRI, genetic and psychometric assessments to identify the mechanisms of pain relief in knee OA patients, following treatments with duloxetine and remifentanil, in a placebo controlled condition. With this we also aim to identify genetic, anatomical and brain activity predictors of treatment outcomes.
The main hypotheses are:
- Analgesic response to duloxetine treatment can be predicted using a range of baseline brain imaging markers and QST.
- Analgesic response to duloxetine is mediated by modulation of neural networks underpinning emotional control.
- Duloxetine-induced changes in brain activation differ between responders and non-responders.
This study is expected to last for two years. It is funded by Arthritis Research United Kingdom and forms part of a wider scientific investigation, using translational methodologies, to enhance the understanding of arthritis pain and to improve its treatment.
|Condition or disease||Intervention/treatment||Phase|
|Osteoarthritis Chronic Pain||Drug: Duloxetine Drug: Remifentanil Drug: Placebo (for Remifentanil) Drug: Placebo (for Duloxetine)||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||77 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Functional Brain Imaging to Understand the Mechanisms of Pain Relief in Knee Osteoarthritis|
|Study Start Date :||December 2014|
|Actual Primary Completion Date :||June 2016|
|Actual Study Completion Date :||June 2016|
Duloxetine 30 mg a day (2 weeks), then 60 mg a day (4weeks), taken by mouth
54 participants will be allocated for duloxetine treatment
Other Name: Cymbalta
Placebo Comparator: Placebo (for Duloxetine)
Sugar pill: 1 capsule a day (2 weeks), then 2 capsules a day (4 weeks) taken by mouth
Drug: Placebo (for Duloxetine)
Sugar pill manufactured to mimic Duloxetine 30mg. 27 participants will be allocated to this intervention
Other Name: Sugar pill
Intravenous infusion with maximum estimated plasma target of 1.0 ng/ml, during less than 20 minutes
27 participants will be allocated to Remifentanil infusion
Other Name: Remifentanil hydrochloride
Placebo Comparator: Placebo (for Remifentanil)
Intravenous infusion of normal saline, during less than 20 min
Drug: Placebo (for Remifentanil)
Placebo comparator to Remifentanil treatment. 27 participants will be allocated to this arm
- Reduction in nociceptive brain response after duloxetine [ Time Frame: Baseline, week six ]
- Neural network change (resting condition) induced by duloxetine [ Time Frame: Baseline, week six ]
- Predicting response to duloxetine from baseline fMRI metrics using univariate and multivariate analysis [ Time Frame: Baseline, week six ]
- Differences in brain response and network change between responders and non-responders [ Time Frame: Baseline, week six ]
- Identification of QST and questionnaire parameters that predict response to duloxetine [ Time Frame: Baseline, week six ]
- Correlation between baseline CPM and TS with brain activity and connectivity changes [ Time Frame: Baseline, week six ]
- Group differences in brain activity and structure in pain processing, limbic and modulatory pathways changes following duloxetine treatment in comparison to placebo [ Time Frame: Baseline, week six ]
- Determination of gene variations that can be linked with duloxetine treatment response [ Time Frame: Baseline, week six ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02208778
|University of Nottingham - School of Medicine - Radiological Sciences|
|Nottingham, Nottinghamshire, United Kingdom, NG7 2UH|
|Principal Investigator:||Dorothee P Auer, PhD||University of Nottingham|