NEUROIMPA "Intraarticular Application of Opioids in Chronic Arthritis"
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •baseline pain score (on a 100 mm Visual Analogue Scale, VAS) >40 mm;
- •male and female patients, age ≥18 - 80 years,
- •body weight 50 - 90 kg.
- •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.
- •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 <
- •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).
- •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.
排除标准
- •Severe cardiovascular, respiratory, metabolic, neurologi-cal, psychiatric disorders; current bacterial infection es-pecially of the knee
- •abuse of analgesics, benzodiazepines, alcohol; "hard drugs"
- •pregnancy, lactation
- •before biopsy thrombocyte count < 100/nl, Quick <50%
- •intake of anticoagulants, anti-aggregants as monothera-py such as ASS 100 will be allowed
- •participation in an investigational trial during the last 30 days or 5 HLT whichever is longer
- •treatment with intraarticular steroids during the past 4 weeks in the selected joint.
- •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.
- •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.
- •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.
研究组 & 干预措施
Morphine Sulfate
Morphine 3 mg intraarticular once at baseline
干预措施: Morphine Sulfate (Drug)
Triamcinolone
Triamcinolone 40 mg intraarticular once at baseline
干预措施: Triamcinolone (Drug)
Placebo
NaCl 0,9% 5 ml intraarticular at baseline
干预措施: placebo (Drug)
结局指标
主要结局
Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline
时间窗: 1 week
Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline
次要结局
- Area under the VAS curve (AUC) of VAS pain during the first week until 8 p.m. on day 7(1 week)
- Pain intensity on McGill pain questionnaire (MPQ) at baseline, week 1 and 2(2 weeks)
- daily activities at baseline, week 1 and 2(2 weeks)
- activity and mobility of the knee joint (Lysholm Gilquist-Score) at baseline, week 1 and 2(2 weeks)
- WOMAC scale (before i.a. injections at baseline, week 1 and 2)(2 weeks)
- 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),(1 weeks)
- supplementary analgesic consumption continuously in the patients diary, recorded at week 1 and 2(2 weeks)
- 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.(Screening, Baseline, week 1, week 2)
研究者
Hildrun Haibel
Priv. Doz. Dr. med. Hildrun Haibel
Charite University, Berlin, Germany