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Ketamine and fMRI for Neuropathic Pain

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ClinicalTrials.gov Identifier: NCT02373449
Recruitment Status : Completed
First Posted : February 27, 2015
Last Update Posted : April 28, 2021
Sponsor:
Information provided by (Responsible Party):
Anuj Bhatia, University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE February 9, 2015
First Posted Date  ICMJE February 27, 2015
Last Update Posted Date April 28, 2021
Study Start Date  ICMJE February 2015
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2015)
Correlation between 'baseline (pre-infusion) fMRI patterns' and 'pain relief (>50% pain reduction, as per NRS or 'Numerical Rating Scale')' [ Time Frame: 1 month following ketamine infusion ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2015)
  • Correlation between 'specific fMRI brain patterns at 1-month post-infusion' and 'change in neuropathic pain intensity (as per NRS) at 3-month post-infusion' [ Time Frame: 3 months following ketamine infusion ]
  • Change in pain intensity at 1 month post-infusion, as measured by Brief Pain Inventory (BPI) [ Time Frame: 1 month following ketamine infusion ]
  • Change in pain intensity at 3 months post-infusion, as measured by Brief Pain Inventory (BPI) [ Time Frame: 3 months following ketamine infusion ]
  • Change in anxiety at 1 month post-infusion, as measured by Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 1 month following ketamine infusion ]
  • Change in anxiety at 3 months post-infusion, as measured by Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 3 months following ketamine infusion ]
  • Change in depression at 1 month post-infusion, as measured by Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 1 month following ketamine infusion ]
  • Change in depression at 3 months post-infusion, as measured by Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 3 months following ketamine infusion ]
  • Change in quality of life at 1 month post-infusion, as measured by Short Form-36 (SF-36) v2 Health Survey [ Time Frame: 1 month following ketamine infusion ]
  • Change in quality of life at 3 months post-infusion, as measured by Short Form-36 (SF-36) v2 Health Survey [ Time Frame: 3 month following ketamine infusion ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine and fMRI for Neuropathic Pain
Official Title  ICMJE Functional Magnetic Resonance Imaging to Predict and Correlate Clinical Outcomes of Ketamine Infusions for Refractory Neuropathic Pain
Brief Summary Neuropathic or nerve injury related pain (NP), an extremely unpleasant condition that is difficult to treat, often has a severe, persistent, and unremitting course. Conventional treatments are often ineffective in relieving NP. Recently, the investigators have developed a cost-efficient regimen involving use of low dose infusions of ketamine for treating neuropathic pain in patients in whom oral medications have failed. We have observed excellent benefits in many of these patients. However, this treatment requires titration and monitoring during the infusion and currently it is not possible to predict which patients will benefit from this intervention. The investigators have shown that functional magnetic resonance imaging (fMRI) of the brain can be used as a tool to predict relief of pain and to assess the effect of treatment in some chronic pain conditions. This innovative project involves development of an fMRI-guided treatment with intravenous ketamine in patients with NP. This study aims to analyze patterns of changes in fMRI of the brain, before and after infusion of ketamine and to correlate the changes with pain intensity. The information from this study will help to deliver this therapy earlier to those patients who are most likely to benefit from ketamine.
Detailed Description This trial is exploratory, prospective, non-randomized, single cohort, single-center, with no blinding of participants, treating physicians, and investigators. Study participants undergo a resting-state fMRI before, after and at '1-month post-ketamine infusion' (standard care). Patients will be recruited over 2 years, from Pain Clinics at Toronto Western Hospital and Mount Sinai Hospital. The primary null hypothesis for this trial is that there are no fMRI brain patterns of patients with neuropathic pain that predict pain relief following ketamine infusion. The secondary null hypothesis for this trial is that there are no correlations between specific fMRI brain patterns of patients with neuropathic pain and change in intensity of pain immediately following ketamine infusion. Further secondary hypothesis include that cortical reorganization in the brain as measured by fMRI at one month after the infusion of ketamine does not correlate with persisting analgesic benefit in patients with neuropathic pain. Finally, we hypothesize that ketamine infusions do not provide significant pain relief, reduction in anxiety and depression, and improvement in quality of life early (at 1 month) and late (at 3 months) after the infusions in patients with neuropathic pain.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Neuralgia
Intervention  ICMJE
  • Other: RS-fMRI
    Resting State-functional Magnetic Resonance Imaging. Protocols involving BOLD (blood oxygen level-dependent) and non-BOLD techniques will be used.
  • Drug: Ketamine
    Part of standard care. To be performed over five consecutive days (Monday to Friday) for six hours per day. A therapeutic range of 0.5 to 2.0 mg/kg/hour is targeted.
Study Arms  ICMJE Experimental: RS-fMRI
All subjects will be instructed to keep their eyes closed but to remain awake during the fMRI measurement. Resting State fMRI (RS-fMRI) will be performed within four weeks of planned infusion of ketamine, immediately after the end of infusion of ketamine on the fifth (last) day of infusion, and on the one month follow-up appointment after the infusion.
Interventions:
  • Other: RS-fMRI
  • Drug: Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 23, 2020)
39
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2015)
40
Actual Study Completion Date  ICMJE December 2020
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Refractory neuropathic pain diagnosed by a >3 score on DN4 (Douleur Neuropathique 4) questionnaire
  • Average daily pain intensity should be moderate or severe, as indicated by a >3 score on NRS (Numerical Rating Scale)
  • Duration of neuropathic pain should be more than three months
  • Participants should have tried at least three medications for neuropathic pain. Each of these medications should belong to a different pharmacological group: anticonvulsants (gabapentin, pregabalin), tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine), serotonin noradrenaline reuptake inhibitors (venlafaxine, duloxetine), tramadol, opioids, cannabinoids, methadone, topical lidocaine and capsaicin patches.

Exclusion Criteria:

  • Ketamine or lidocaine intravenous infusion within the 6 months preceding enrollment into this trial
  • Contraindications to ketamine (allergy, pregnancy, uncontrolled arterial hypertension, uncontrolled hyperthyroidism, severe ischemic heart disease or heart failure, severe liver or kidney disease, space occupying lesion in the brain or the spinal cord, uncontrolled epilepsy and glaucoma)
  • Ongoing litigation issues related to the patient's pain that may affect reporting of pain and quality of life
  • An unstable medical or psychiatric condition that makes it unsafe to use study medications
  • Participants unable to comply with the study protocol (e.g. follow-up visits, filling forms for measuring anxiety, depression, and quality of life)
  • Relative (claustrophobia) or absolute contraindications for MRI
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02373449
Other Study ID Numbers  ICMJE 14-8706-AE
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Anuj Bhatia, University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anuj Bhatia UHN
PRS Account University Health Network, Toronto
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP