NEUROIMPA - Intraarticular Application of Opioids in Chronic Arthritis of the Knee Joint

NEUROIMPA "Intraarticular Application of Opioids in Chronic Arthritis"

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Knee Arthritis
• Intervention / Treatment: Drug: placebo; Drug: Morphine Sulfate; Drug: Triamcinolone

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.

• Study Type: Interventional
• Enrollment (Anticipated): 112
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Charité CBF Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Morphine Sulfate; Morphine 3 mg intraarticular once at baseline	Drug: Morphine Sulfate; active intervention; Other Names: Morphin Hexal
Active Comparator: Triamcinolone; Triamcinolone 40 mg intraarticular once at baseline	Drug: Triamcinolone; active control; Other Names: Triamcinolon Liechtenstein
Placebo Comparator: Placebo; NaCl 0,9% 5 ml intraarticular at baseline	Drug: placebo; placebo control; Other Names: NaCl 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline	Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the VAS curve (AUC) of VAS pain during the first week until 8 p.m. on day 7	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	Pain intensity on McGill pain questionnaire (MPQ) at baseline, week 1 and 2	2 weeks
daily activities at baseline, week 1 and 2	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	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)	WOMAC scale (before i.a. injections and at the end of each week)	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),	nflammatory parameters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFα) in synovial biopsies and fluid (before and 7 days af-ter i.a. medication),	1 weeks
supplementary analgesic consumption continuously in the patients diary, recorded at week 1 and 2	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.	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 2.	Screening, Baseline, week 1, week 2

Collaborators and Investigators

• Sponsor: Hildrun Haibel
• Collaborators: DLR German Aerospace Center
• Investigators: Principal Investigator: Hildrun Haibel, PD Dr, Charité CBF, Rheumatology, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: November 10, 2016
• First Submitted That Met QC Criteria: November 15, 2016
• First Posted (Estimate): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: knee arthritis, morphine, local injection, pain
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Analgesics, Opioid; Narcotics; Triamcinolone; Morphine
• Other Study ID Numbers: NEUROIMPA2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: no plan