Application into the joint of opioids in chronic arthritis of the knee joint

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2015-000538-31-DE
• Date of registration: 07/04/2015
• Prospective Registration: Yes
• Primary sponsor: Charité University medicine Berlin
• Public title: Application into the joint of opioids in chronic arthritis of the knee joint
• Scientific title: NEUORIMPA - Intraarticular Application of Opioids in Chronic Arthritis of the knee joint - Neuroimpa - knee joint
• Date of first enrolment: 01/06/2015
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000538-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Trial Coordinator
• Affiliation: Charité Campus Benjamin Franklin Department of Rheumatology

• Name: Trial Coordinator
• Affiliation: Charité Campus Benjamin Franklin Department of Rheumatology

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria:
1. Clinically detectable and/or ultrasound-visible knee ef-fusion as part of spondyloarthritis (Assessments in SpondyloArthritis international Society, ASAS criteria), Rheumatoid Arthritis, RA (according to American Col-lege of Rheumatology, ACR criteria), undifferentiated mono- or oligoarthritis, Osteoarthritis of the knee, OA.
2. baseline pain score (on a 100 mm Visual Analogue Scale, VAS) >40 mm;
3. male and female patients, age =18 - 80 years,
4. body weight 50 - 90 kg.
5. Able and willing to give a written informed consent and comply with the requirements of the study protocol.Only patients who give written informed consent will be included in the trial.
6. If female: either not of child-bearing potential (meno-pausal since 1 year or surgically sterile) or is willing and able to practice a reliable method of contraception throughout the study with a pearl index <1. Reliable methods of contraception are: condoms plus other methods: implants, injecatbles, combined oral contracep-tives, intrauterine devices, initiated at least 90 days prior to screening. Further reliable methods are a vasecto-mised partner (at least 1 year prior to enrolment), sexual-ly abstinent, surgically sterilized (including hysterecto-my), postmenopausal defined as at least 1 year of spon-taneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/l and estradiol below 30 nl/l is confirmatory).
7. If male: either not of child-bearing potential (surgically sterilized, e.g. vasectomy) or is willing and able to prac-tice a reliable method of contraception with a pearl index <1 (see inclusion criterium 6) throughout the study.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion criteria:
Exclusion criteria:
1. Severe cardiovascular, respiratory, metabolic, neurologi-cal, psychiatric disorders; current bacterial infection es-pecially of the knee
2. abuse of analgesics, benzodiazepines, alcohol; “hard drugs”
3. pregnancy, lactation
4. before biopsy thrombocyte count < 100/nl, Quick <50%
5. intake of anticoagulants, anti-aggregants as monothera-py such as ASS 100 will be allowed
6. participation in an investigational trial during the last 30 days or 5 HLT whichever is longer
7. treatment with intraarticular steroids during the past 4 weeks in the selected joint.
8. Patients with a history of a severe psychiatric illness, which might interfere with the patient's ability to under-stand the requirements of the study and assessment.
9. Patients who are institutionalised due to regulatory or juridical order. Patients who are an employee of the in-vestigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
10. Known hypersensitivity to any component of the study medication to morphine or triamcinolone, ileus, respira-tory depression, severe chronic obstructive airway dis-eases, acute abdomen, coagulopathy and/ or infections of the injection site, instability of the injected joint, psori-atic skin manifestation at the injection site, periarticular calcification, non-vascularized bone necrosis, tendon rupture, Charcot-joint.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

chronic arthritis of the knee joint effusion as part of spondyloarthritis (Assessments in SpondyloArthritis international Society, ASAS criteria), Rheumatoid Arthritis, RA (according to American Col-lege of Rheumatology, ACR criteria), undifferentiated mono- or oligoarthritis, Osteoarthritis of the knee, OA.
MedDRA version: 18.0 Level: LLT Classification code 10067624 Term: Knee arthritis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Morphine Hexal
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Morphinsulfat
Other descriptive name: MORPHINE SULFATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Triam 40 mg Lichtenstein
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: TRIAMCINOLONACETONID
Other descriptive name: TRIAMCINOLONACETONID EP
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 1

Primary end point(s): Primary efficacy endpoint:
Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline.

Main Objective: To investigate pain and inflammatory parameters (cytokines, immune cells) in knee joint tissue of chronic arthritis pa-tients following intraarticular (i.a.) injections of morphine, a standard steroid or placebo.
The primary hypothesis is that i.a. morphine results in sig-nificantly lower pain scores and supplemental analgesic consumption than placebo during the first week after injec-tion, an efficacy comparable to standard i.a. steroid (tri-amcinolone) medication.
Primary efficacy endpoint:
Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline.

Secondary Objective: Key secondary endpoint(s):
Area under the VAS curve (AUC) during the first week until 8 p.m. on day 7. Pain intensity on McGill pain questionnaire (MPQ); daily activities; activity and mobility of the knee joint (Lysholm Gilquist-Score); WOMAC scale (before i.a. injec-tions and at the end of each week). Inflammatory parame-ters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFa) in synovial biopsies and fluid (before and 7 days af-ter i.a. medication), supplementary analgesic consumption.
Assessment of safety:
Any systemic (e.g. nausea, sedation) and local side effects (infection, tissue injury) will be recorded.

Secondary Outcome(s)

Secondary end point(s): Area under the VAS curve (AUC) during the first week until 8 p.m. on day 7. Pain intensity on McGill pain questionnaire (MPQ); daily activities; activity and mobility of the knee joint (Lysholm Gilquist-Score); WOMAC scale (before i.a. injec-tions and at the end of each week). Inflammatory parame-ters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFa) in synovial biopsies and fluid (before and 7 days af-ter i.a. medication), supplementary analgesic consumption.
Assessment of safety:
Any systemic (e.g. nausea, sedation) and local side effects (infection, tissue injury) will be recorded.

Timepoint(s) of evaluation of this end point: week 1, week 2, safety follow up week 3

Secondary ID(s)

Neuroimpa2015

Source(s) of Monetary Support

Bundesministerium für Bildung und Forschung

Ethics review

Status: Approved
Approval date: 01/06/2015
Contact: