Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effectiveness of Ketamine Administered by Mesotherapy in Complex Regional Pain Syndrome Type 1 (CRPS1) (MESO-SDRC)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04650074
Recruitment Status : Not yet recruiting
First Posted : December 2, 2020
Last Update Posted : June 4, 2021
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE November 25, 2020
First Posted Date  ICMJE December 2, 2020
Last Update Posted Date June 4, 2021
Estimated Study Start Date  ICMJE September 1, 2021
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2020)
Visual Analogue Scale (VAS) score [ Time Frame: On day 0 (inclusion) and day 60 (end of patient follow-up) ]
Pain measured by VAS (Visual Analogue Scale)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2020)
  • Evolution of the Visual Analogue Scale score [ Time Frame: On day 0 (inclusion), on day 1, day 7, day 14 and day 30 (mesotherapy sessions), and on day 60 (end of patient follow-up) ]
    The VAS (Visual Analogue Scale) score will be assessed at inclusion, before each mesotherapy session, and at the end of the patient follow-up
  • Neuropathic Pain Symptom Inventory (NPSI) self-questionnaire score [ Time Frame: On day 0 (inclusion), on day 1, day 7, day 14 and day 30 (mesotherapy sessions), and on day 60 (end of the patient follow-up) ]
    The Neuropathic pain will be assessed using the NPSI (Neuropathic Pain Symptom Inventory self-questionnaire) at inclusion, before each mesotherapy session, and at the patients withdrawal.
  • Brief Pain Inventory (BPI) self-questionnaire score [ Time Frame: On day 0 (inclusion) and on day 60 (end of patient follouw-up) ]
    The main dimensions of pain (i.e. intensity, functional disability, social and family repercussions as well as the level of psychological distress) will be assessed using the BPI (Brief Pain Inventory self-questionnaire) at inclusion and at the patients withdrawal.
  • Relevant adverse events [ Time Frame: Until day 60 (end of patient follow-up) ]
    The relevant adverse events (AEs), as well as the average of the highest grades of the relevant adverse events, will be collected during the patient follow-up, in particular after each mesotherapy session. The physician will ask the patient at each of the visits and will report any adverse event (AE). The nature and intensity of the AE will be assessed according to the Common Terminology Criteria for Adverse Events grid (CTCAE version 5.0). Relevant adverse events (AEs at least possibly related to treatment or mesotherapy) will be considered.
  • Concomitant consumption of analgesics [ Time Frame: Until day 60 (end of patient follow-up) ]
    The consumption of other analgesics concomitant with the treatment will be recorded
  • EQ-5D-5L (EuroQol health states) questionnaire score [ Time Frame: On day 1 (inclusion) and on day 60 (end of patient follow-up) ]
    The quality of life will be assessed using the EQ-5D-5L questionnaire (EuroQol health states)
  • Visual Analogue Scale and Adverse Events grades (Benefit / risk balance) [ Time Frame: Until day 60 (end of patient follow-up) ]
    To simultaneously compare the VAS (Visual Analogue Scale) and the relevant adverse events (AE) grades between groups. This benefit-risk balance will be estimate in a hierarchical fashion using the method of pairwise comparisons. The VAS will be used as the first endpoint (benefit) and the highest grade of AE in a given patient as the second endpoint (risk). No clinical relevance threshold will be specified for the two criteria for the primary analysis, but they will then be added as a sensitivity analysis.
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 Effectiveness of Ketamine Administered by Mesotherapy in Complex Regional Pain Syndrome Type 1 (CRPS1)
Official Title  ICMJE Pilot Study to Evaluate the Effectiveness of a Mixture of Ketamine / Lidocaine Administered by Mesotherapy in the Management of Neuropathic Pain in Complex Regional Pain Syndrome Type 1 (CRPS1). A Monocentric Randomized and Controlled Clinical Study
Brief Summary

Complex Regional Pain Syndrome type 1 (CRPS1) is a disabling pain syndrome. Its definitive treatment has not been established and the results of current treatments are often unsatisfactory.

The prognosis is difficult to establish because the vast majority of CRPS regresses within a few weeks. However, some forms are hyperalgesic with a major chronic painful picture, very debilitating and responding poorly to treatments with possible permanent sequelae.

The management of CRPS remains difficult and unsatisfactory and is symptomatic, multidimensional and multidisciplinary involving medical, paramedical and socio-professional workers. The priority therapeutic objectives are analgesia, maintenance or gain of joint range and maintenance or restoration of motor functions. This treatment is not the subject of a consensus and its implementation is sometimes the responsibility of specialized centers such as "pain relief" centers or even Physical Medicine and Rehabilitation (MPR) structures.

Previous studies using ketamine as a treatment for CRPS1 show encouraging results with a decrease in neuropathic pain. Ketamine is a low dose pain reliever. Ketamine has been studied as an adjuvant for the treatment of chronic pain, particularly neuropathic pain. The results suggest that ketamine decreases pain intensity and reduces opioid reliance when used as an adjunct to chronic and acute pain. Ketamine is believed to have a greater analgesic effect in patients with CRPS1 compared to other chronic pain syndromes. In these studies, ketamine was used intravenously, subcutaneously, orally, intranasally, or topically.

Mesotherapy allows microdose local treatment to be carried out limiting side effects, ensuring compliance and easy to implement. The injected solutions often contain a local anesthetic (procaine or lidocaine). It allows better local tolerance from the start of treatment. In addition, through its vasodilator effect on the microcirculation, it increases the effectiveness and tolerance of other injected products.

There are no studies using ketamine administrated by mesotherapy. Based on the scientific literature, there are good reasons to believe that this treatment could be effective on the neuropathic pain of CRPS1 and well tolerated.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuropathic Pain
  • Complex Regional Pain Syndrome Type 1
Intervention  ICMJE
  • Drug: LIDOCAINE 20 mg

    4 injections (on day 1, day 7, day 14, day 30) by mesotherapy of 20 mg Lidocaine (qsp 6 ml NaCl 0.9%).

    Each mesotherapy session includes 2 steps performed chronologically. It will be done within 2 or 3 minutes each one:

    • 1st sequence: intra-epidermal injections of 3 ml by manual technique in crossed lines with a 13 mm x 0.30 needle,
    • 2nd sequence : superficial intradermal injections of 3 ml (between 1 and 2 mm) using a technique assisted by a Pistor Eliance injector at a frequency of 200 punctures per minute.
  • Drug: LIDOCAINE 20 mg + KETAMINE 20 mg

    4 injections (on day 1, day 7, day 14, day 30) by mesotherapy of 20 mg Lidocaine + 20 mg Ketamine (qsp 6 ml NaCl 0.9%).

    Each mesotherapy session includes 2 steps performed chronologically. It will be done within 2 or 3 minutes each one:

    • 1st sequence: intra-epidermal injections of 3 ml by manual technique in crossed lines with a 13 mm x 0.30 needle,
    • 2nd sequence : superficial intradermal injections of 3 ml (between 1 and 2 mm) using a technique assisted by a Pistor Eliance injector at a frequency of 200 punctures per minute.
  • Drug: LIDOCAINE 20 mg + KETAMINE 40 mg

    4 injections (on day 1, day 7, day 14, day 30) by mesotherapy of 20 mg Lidocaine + 40 mg Ketamine (qsp 6 ml NaCl 0.9%).

    Each mesotherapy session includes 2 steps performed chronologically. It will be done within 2 or 3 minutes each one:

    • 1st sequence: intra-epidermal injections of 3 ml by manual technique in crossed lines with a 13 mm x 0.30 needle,
    • 2nd sequence : superficial intradermal injections of 3 ml (between 1 and 2 mm) using a technique assisted by a Pistor Eliance injector at a frequency of 200 punctures per minute
Study Arms  ICMJE
  • Active Comparator: LIDOCAINE 20 mg
    4 injections (on day 1, day 7, day 14, day 30) by mesotherapy of 20 mg Lidocaine (qsp 6 ml NaCl 0.9%).
    Intervention: Drug: LIDOCAINE 20 mg
  • Experimental: LIDOCAINE 20 mg + KETAMINE 20 mg
    4 injections (on day 1, day 7, day 14, day 30) by mesotherapy of 20 mg Lidocaine + 20 mg Ketamine (qsp 6 ml NaCl 0.9%).
    Intervention: Drug: LIDOCAINE 20 mg + KETAMINE 20 mg
  • Experimental: LIDOCAINE 20 mg + KETAMINE 40 mg
    4 injections (on day 1, day 7, day 14, day 30) by mesotherapy of 20 mg Lidocaine + 40 mg Ketamine (qsp 6 ml NaCl 0.9%).
    Intervention: Drug: LIDOCAINE 20 mg + KETAMINE 40 mg
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 25, 2020)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2022
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male / female aged ≥18 years,
  • Patient suffering from Complex Regional Pain Syndrome Type 1 (CRPS1), according to the Budapest criteria, with a neuropathic component limited to the lower limbs diagnosed by the Neuropathic pain DN4 Questionnaire
  • Patient having undergone a three-stage dynamic bone scan: vascular, tissue, bone, showing diffuse and extensive hypofixation in the area suspected of CRPS1,
  • Negative urinary pregnancy test in women of childbearing age,
  • VAS (Visual Analogue Scale) > 50mm (on a scale of 0 to 100 mm) at inclusion,
  • Patients affiliated to the French social security system,
  • Writing informed consent obtained.

Exclusion Criteria:

  • Patient with the following medical history or ongoing pathologies: epilepsy, hypertension (> 180mm / 100mm Hg), unbalanced coronary artery disease, recent myocardial infarction (MDI) (less than 12 months), porphyria, hyperthyroidism, known Behçet's disease, known blood crass disorder or PT (Prothrombin Time) <20%, known psychiatric disorders, known septic osteoarticular disease,
  • Patient with HIV ((Human Immunodeficiency Viruses) infection, immunosuppression and / or immunosuppressive treatment
  • Severe heart failure,
  • History of severe allergy (angioedema),
  • Known allergies to Cr and Zn,
  • Current skin infection,
  • Skin lesion next to the injection area
  • Phobia of injections,
  • Known hypersensitivity to ketamine hydrochloride or chlorobutanol,
  • Known hypersensitivity to lidocaine hydrochloride or to amide-linked local anesthetics,
  • Pregnant or breastfeeding woman
  • Patient under protective measure (safeguard measure, curatorship, guardianship) or deprived of liberty.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Philippe LAFUMA, MD 472 110 444 ext +33 Philippe.lafuma@chu-lyon.fr
Contact: Laurent MAGAUD, MD 472 112 805 ext +33 laurent.magaud@chu-lyon.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04650074
Other Study ID Numbers  ICMJE 69HCL18_0996
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Hospices Civils de Lyon
Verification Date June 2021

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