Clinical trial NCT02967302: NEUROIMPA - Intraarticular Application of Opioids in Chronic Arthritis of the Knee Joint
Official title: NEUROIMPA "Intraarticular Application of Opioids in Chronic Arthritis"
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Knee Arthritis
Keywords: knee arthritis, morphine, local injection, pain
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: DLR German Aerospace Center
First posted: 2016-11-18
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate pain and inflammatory parameters (cytokines, immune cells) in knee joint tissue of chronic arthritis patients following intraarticular (i.a.) injections of morphine, a standard steroid or placebo.

The primary hypothesis is that i.a. morphine results in significantly lower pain scores and supplemental analgesic consumption than placebo during the first week after injection, an efficacy comparable to standard i.a. steroid (triamcinolone) medication.

Detailed description: 3 arm, double blind, placebo controlled, prospective, mo-nocenter study, which will be conducted in the Department of Rheumatology, Charité University Medicine Berlin, Cam-pus Benjamin Franklin in collaboration with several rheu-matology and orthopedic practices in the Berlin area. Ultra-sound guided synovial needle biopsy and interventions will only be performed at CBF.

Eligible patients will be treated with either morphine 3 mg i.a., NaCl 0.9% i.a. or triamcinolone 40 mg i.a. at Baseline. The entire study period will be 2 weeks per patient.

Assessment of the primary outcome parameter will be at week 1. The patients will be monitored closely throughout the entire study period with a total of 4 visits (screening, baseline, week 1, week 2).

Safety data will be collected in the adverse events form, vital parameters, physical examination and laboratory tests dur-ing the whole study.

Eligibility 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 in-cluded 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.

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.

Primary outcomes:
measure: Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline
timeFrame: 1 week
Secondary outcomes:
measure: Area under the VAS curve (AUC) of VAS pain during the first week until 8 p.m. on day 7
timeFrame: 1 week
measure: Pain intensity on McGill pain questionnaire (MPQ) at baseline, week 1 and 2
timeFrame: 2 weeks
measure: daily activities at baseline, week 1 and 2
timeFrame: 2 weeks
measure: activity and mobility of the knee joint (Lysholm Gilquist-Score) at baseline, week 1 and 2
timeFrame: 2 weeks
measure: WOMAC scale (before i.a. injections at baseline, week 1 and 2)
timeFrame: 2 weeks
measure: nflammatory parameters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFα) in synovial biopsies and fluid (before i.a. medication at baseline and week 1),
timeFrame: 1 weeks
measure: supplementary analgesic consumption continuously in the patients diary, recorded at week 1 and 2
timeFrame: 2 weeks
measure: Any systemic (e.g. nausea, sedation) and local side effects (infection, tissue injury) will be recorded continuously in the patients diary, recorded at week 1 and week 2.
timeFrame: Screening, Baseline, week 1, week 2
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité CBF Rheumatology
Study officials:
affiliation: Charité CBF, Rheumatology, Berlin, Germany
name: Hildrun Haibel, PD Dr
role: PRINCIPAL_INVESTIGATOR
References: