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

NCT04650074 | Completed Phase 2

• 1 other identifier: 69HCL18_0996
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuropathic Pain; Complex Regional Pain Syndrome Type 1

Keywords

Complex Regional Pain Syndrome Type 1; Mesotherapy; Lidocaïne; Ketamine; Randomized clinical trial

Outcome Measures

Primary Outcomes (1)

• Visual Analogue Scale (VAS) score

  Pain measured by VAS (Visual Analogue Scale)

  On day 0 (inclusion) and day 56 (end of patient follow-up)

Secondary Outcomes (7)

• Evolution of the Visual Analogue Scale score

  On day 0 (inclusion), on day 1, day 7, day 14 and day 28 (mesotherapy sessions), and on day 56 (end of patient follow-up)

• Neuropathic Pain Symptom Inventory (NPSI) self-questionnaire score

  On day 0 (inclusion), on day 1, day 7, day 14 and day 28 (mesotherapy sessions), and on day 56 (end of the patient follow-up)

• Brief Pain Inventory (BPI) self-questionnaire score

  On day 0 (inclusion) and on day 56 (end of patient follouw-up)

• Relevant adverse events

  Until day 56 (end of patient follow-up)

• Concomitant consumption of analgesics

  Until day 56 (end of patient follow-up)

Study Arms (3)

LIDOCAINE 20 mg

ACTIVE COMPARATOR

4 injections (on day 1, day 7, day 14, day 28) by mesotherapy of 20 mg Lidocaine (qsp 6 ml NaCl 0.9%).

Drug: LIDOCAINE 20 mg

LIDOCAINE 20 mg + KETAMINE 20 mg

EXPERIMENTAL

4 injections (on day 1, day 7, day 14, day 28) by mesotherapy of 20 mg Lidocaine + 20 mg Ketamine (qsp 6 ml NaCl 0.9%).

Drug: LIDOCAINE 20 mg + KETAMINE 20 mg

LIDOCAINE 20 mg + KETAMINE 40 mg

EXPERIMENTAL

4 injections (on day 1, day 7, day 14, day 28) by mesotherapy of 20 mg Lidocaine + 40 mg Ketamine (qsp 6 ml NaCl 0.9%).

Drug: LIDOCAINE 20 mg + KETAMINE 40 mg

Interventions

LIDOCAINE 20 mg DRUG

4 injections (on day 1, day 7, day 14, day 28) 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.

LIDOCAINE 20 mg

LIDOCAINE 20 mg + KETAMINE 20 mg DRUG

4 injections (on day 1, day 7, day 14, day 28) 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.

LIDOCAINE 20 mg + KETAMINE 20 mg

LIDOCAINE 20 mg + KETAMINE 40 mg DRUG

4 injections (on day 1, day 7, day 14, day 28) 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

LIDOCAINE 20 mg + KETAMINE 40 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 or upper limbs diagnosed by the Neuropathic pain DN4 Questionnaire
• Patient having undergone a three-stage dynamic bone scan less than 3 months old : vascular, tissue, bone, showing diffuse and extensive hyperfixation in the area suspected of CRPS1,
• Negative urinary pregnancy test in women of childbearing age,
• Patients affiliated to the French social security system,
• Writing informed consent obtained.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Department of orthopedic surgery and trauma emergencies of the lower limb, Edouard Herriot Hospital, Hospices Civils de Lyon

Lyon, 69437, France

Location

MeSH Terms

Conditions

Neuralgia; Complex Regional Pain Syndromes

Interventions

Lidocaine; Ketamine

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Autonomic Nervous System Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 2, 2020
• Study Start: November 5, 2021
• Primary Completion: January 12, 2024
• Study Completion: January 12, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

FR (1)