Comparing the effects of two pain relievers on inflammation in healthy volunteers
| ISRCTN | ISRCTN13358268 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13358268 |
- Submission date
- 04/11/2024
- Registration date
- 18/12/2024
- Last edited
- 18/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
This study aims to test a new type of pain reliever called NCX 701, which is designed to be easier on the stomach than regular acetaminophen (paracetamol). Researchers want to see if NCX 701 is effective and well-tolerated, and if it can reduce inflammation in a controlled setting.
Who can participate?
Healthy male volunteers aged 18-45 years can participate in this study.
What does the study involve?
Participants will be randomly assigned to receive either NCX 701, regular acetaminophen, or a placebo. They will take a single oral dose of the assigned treatment before being given a small amount of a substance (LPS) that causes mild inflammation. The study is double-blind, meaning neither the participants nor the researchers know who is receiving which treatment.
What are the possible benefits and risks of participating?
Participants may help in the development of a new, potentially safer pain reliever. Risks include possible side effects from the treatments and the mild inflammation caused by LPS.
Where is the study run from?
The study is conducted at the Medical University of Vienna (Austria)
When is the study starting and how long is it expected to run for?
June 2002 to January 2003.
Who is funding the study?
Not applicable (company does not exist any more)
Who is the main contact?
Dr Sophie Brunner-Ziegler, sophie.brunner-ziegler@meduniwien.ac.at
Contact information
Public, Scientific, Principal Investigator
währinger Gürtel 18-20
Vienna
1090
Austria
 ORCID ID |
0000-0001-7825-1254 |
|---|---|
| Phone | +43 4040046710 |
| sophie.ziegler@meduniwien.ac.at |
Study information
| Study design | Placebo controlled randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment, Safety, Efficacy |
| Participant information sheet | 46340 PIS 13.05.2022 NCX701-x-106_Einverstaendniserklaerung.pdf |
| Scientific title | Effects of Acetaminophen and NO-Acetaminophen (NCX 701) in human endotoxemia: a randomized, placebo-controlled trial in healthy volunteers |
| Study objectives | For the human setting, the gastrointestinal-sparing effect of similar NO-derivations of aspirin was confirmed in several pharmacodynamic (PD) studies on inflammation and coagulation biomarkers. Enhanced potency and improved safety were attributed to multifactorial benefits of supplementing the NO-moiety to the parent compound, including anti-proliferative efficacy, endothelium protection, increased blood flow and COX- sparing besides the anti-inflammatory activity. Based on these observations it seemed reasonable to test if a beneficial influence on the pharmacological activity might be obtained as well, if a NO-moiety is added to acetaminophen. It was anticipated that developing NO-acetaminophen (“NCX 701”) might open new perspectives in the treatment of pain. |
| Ethics approval(s) |
Approved 01/06/2002, Ethics Committee of the Medical University of Vienna (Borschkegasse, Vienna, 1090, Austria; +43 1 40 400 21 460; ethik-kom@meduniwien.ac.at), ref: not applicable |
| Health condition(s) or problem(s) studied | Inflammatory status |
| Intervention | After giving written informed consent eligible subjects were hospitalized at the clinical site on day 0 and fed with 3 meals and water to control dietary nitrate intake until the following morning (day 1). On day 1, after overnight fasting, participants received their randomized treatment (1g NCX 701, 2 g NCX 701, 1g acetaminophen or placebo) orally after suspension in at least 180 mL of water. Intake of study medication was scheduled 60 minutes before lipopolysaccharide (LPS) infusion under the supervision of the clinical team. Volunteers were allowed to leave the study site eight hours after LPS infusion and were requested to return in the morning of the following day (day 2) for blood sampling for PD analysis and reporting of adverse events. One week after LPS infusion a final follow-up visit was scheduled for the morning of day 8. During this visit PD parameters were analysed again and adverse events were recorded once more. Randomisation process by sealed envelope |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | NO-paracetamol (NCX-701) |
| Primary outcome measure | 1. Interleukin (IL)-6 is measured using high sensitivity enzyme immunoassays at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 2. Interleukin (IL)-8 is measured using high sensitivity enzyme immunoassays at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 3. Monocyte chemoattractant protein-1 (MCP-1) is measured using enzyme-immunoassay at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 4. Tumor necrosis factor-alpha (TNF-alpha) is measured using high sensitivity enzyme immunoassays at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 5. Soluble vascular cell adhesion protein-1 (VCAM-1) is measured using high sensitivity enzyme immunoassays at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 6. Soluble E-selectin is measured using high sensitivity enzyme immunoassays at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 |
| Secondary outcome measures | 1. Matrix metalloproteinase-2 (MMP-2) is measured using enzyme immune assays (R&D Systems) at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 2. Matrix metalloproteinase-9 (MMP-9) is measured using enzyme immune assays (R&D Systems) at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 3. White blood counts (WBC) are measured using a cell counter (Sysmex, Milton Keynes, UK) at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 4. Elastase is measured at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 5. Von Willebrand Factor (VWF) is measured using turbidometry with a commercial kit from Behring (Marburg, Germany) at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, 7 hours after LPS infusion, day 2, and day 8 6. Platelet counts are measured using a cell counter (Sysmex, Milton Keynes, UK) at baseline, 1 hour before LPS infusion, 2, 3, 4, 5, and 7 hours after LPS infusion, day 2, and day 8 7. ECG is measured every 15 minutes during the first 6 hours after endotoxin bolus infusion 8. Heart rate is measured every 15 minutes during the first 6 hours after endotoxin bolus infusion 9. Oxygen saturation is measured every 15 minutes during the first 6 hours after endotoxin bolus infusion 10. Lying blood pressure is measured every 15 minutes during the first 6 hours after endotoxin bolus infusion 11. Routine blood analysis is measured one week after endotoxin bolus infusion (day 8) 12. Occurrence of adverse events is monitored throughout the entire study period, including day 2 and day 8 follow-up visits |
| Overall study start date | 01/06/2002 |
| Completion date | 01/01/2003 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Male |
| Target number of participants | 40 |
| Total final enrolment | 40 |
| Key inclusion criteria | Healthy male volunteers aged 18-45 years |
| Key exclusion criteria | Does not meet inclusion criteria |
| Date of first enrolment | 01/08/2002 |
| Date of final enrolment | 01/10/2002 |
Locations
Countries of recruitment
- Austria
Study participating centre
Vienna
1090
Austria
Sponsor information
Hospital/treatment centre
Währinger Gürtel 18-20
wien
1090
Austria
| Phone | +43 4040046710 |
|---|---|
| bernd.jilma@meduniwien.ac.at | |
| Website | http://www.meduniwien.ac.at/homepage/1/homepage/ |
"ROR" |
https://ror.org/05n3x4p02 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 01/01/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to data protection reasons and based on a previous agreement with the volunteers. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | in German | 13/05/2022 | 08/11/2024 | No | Yes |
Additional files
Editorial Notes
08/11/2024: Trial's existence confirmed by Ethics Committee of the Medical University of Vienna.
