Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Imaging Pain Relief in Osteoarthritis (IPRO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02208778
Recruitment Status : Completed
First Posted : August 5, 2014
Last Update Posted : November 27, 2017
Sponsor:
Collaborator:
Arthritis Research UK
Information provided by (Responsible Party):
University of Nottingham

Brief Summary:

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Duloxetine
Duloxetine 30 mg a day (2 weeks), then 60 mg a day (4weeks), taken by mouth
Drug: Duloxetine
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

Experimental: Remifentanil
Intravenous infusion with maximum estimated plasma target of 1.0 ng/ml, during less than 20 minutes
Drug: Remifentanil
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
Other Names:
  • Sodium chloride
  • Normal saline




Primary Outcome Measures :
  1. Reduction in nociceptive brain response after duloxetine [ Time Frame: Baseline, week six ]
  2. Neural network change (resting condition) induced by duloxetine [ Time Frame: Baseline, week six ]
  3. Predicting response to duloxetine from baseline fMRI metrics using univariate and multivariate analysis [ Time Frame: Baseline, week six ]
  4. Differences in brain response and network change between responders and non-responders [ Time Frame: Baseline, week six ]

Secondary Outcome Measures :
  1. Identification of QST and questionnaire parameters that predict response to duloxetine [ Time Frame: Baseline, week six ]
  2. Correlation between baseline CPM and TS with brain activity and connectivity changes [ Time Frame: Baseline, week six ]
  3. 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 ]

Other Outcome Measures:
  1. Determination of gene variations that can be linked with duloxetine treatment response [ Time Frame: Baseline, week six ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   35 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Radiographically defined OA knee changes with knee pain
  • Must have self-reported knee pain
  • Able to give informed consent
  • Over 35 years old
  • Male or female
  • Females not pregnant or lactating and using effective contraception

Exclusion Criteria:

  • People with any known contraindication to MRI like

    • Intraocular metallic foreign bodies;
    • Intracranial aneurysm clips;
    • Cardiac pacemakers and defibrillators;
    • Cochlear implants;
  • People with a significant head tremor;
  • People with potential metal foreign bodies due to previous accidents;
  • Breastfeeding or pregnancy, confirmed by pregnancy test;
  • People that are felt to be unfit for the MRI scan according to the judgement of medically qualified personnel, either on the research team, or the patient's clinical team. (eg. due to back pain, claustrophobia, acute sickness etc.) This includes patients with signs of impaired temperature regulation such as an extremely high fever;
  • Patients with large tattoos, specifically in the head, neck or shoulder region;
  • Persons that do not have the capacity to consent;
  • Aged less than 35;
  • Major medical, neurological and psychiatric co-morbidities;
  • Other significant medical condition;
  • Metallic agents embedded within the body (ie. Shrapnel, surgical pins);
  • Refusal by participant to general practitioner (GP) being informed;
  • Have uncontrolled narrow-angle glaucoma;
  • Have recently taken monoamine oxidase inhibitor (MAOI) or Mellaril® (thioridazine);
  • Taking fluvoxamine, ciprofloxacin or enoxacin;
  • Taking St. John's Wort, a herbal treatment (Hypericum perforatum);
  • Taking other medicines containing duloxetine;
  • Have liver disease or severe kidney disease;
  • Currently on antidepressant treatment, including treatment for pain with tricyclic agents such as amitryptiline;
  • Have recently taken monoamine oxidase inhibitor (MAOI) or Mellaril® (thioridazine);
  • Taking tramadol;
  • Known hypersensitivity, allergy or intolerance to one of duloxetine's components;
  • Unwillingness to take caution in relation to use of other centrally active substances such as alcohol and sedative drugs;
  • Current treatment with potent inhibitors of CYP1A2 like fluvoxamine;

Participants undergoing acute treatment (remifentanil or placebo) have, in addition to the stated above, the following exclusion criteria:

  • Taking morphine
  • Known hypersensitivity, allergy or intolerance to one of remifentanil's components or other fentanyl - analogues
  • Current treatment with cardiac depressant drugs such as beta-blockers and calcium channel blocking agents

Information from the National Library of Medicine

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


Locations
Layout table for location information
United Kingdom
University of Nottingham - School of Medicine - Radiological Sciences
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
Arthritis Research UK
Investigators
Layout table for investigator information
Principal Investigator: Dorothee P Auer, PhD University of Nottingham

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT02208778     History of Changes
Other Study ID Numbers: 13124
First Posted: August 5, 2014    Key Record Dates
Last Update Posted: November 27, 2017
Last Verified: May 2017

Keywords provided by University of Nottingham:
Osteoarthritis
Chronic Pain
Pain relief

Additional relevant MeSH terms:
Layout table for MeSH terms
Physiological Effects of Drugs
Osteoarthritis
Chronic Pain
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Remifentanil
Duloxetine Hydrochloride
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Antidepressive Agents
Psychotropic Drugs
Dopamine Agents