Mechanisms of N-acetylcysteine Mediated Vascular Adverse Effects
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01209455|
Recruitment Status : Unknown
Verified September 2010 by University of Edinburgh.
Recruitment status was: Recruiting
First Posted : September 27, 2010
Last Update Posted : July 19, 2011
|Condition or disease||Intervention/treatment||Phase|
|Poisoning||Drug: Chlorphenamine and Ranitidine Drug: Paracetamol||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Mechanisms of N-acetylcysteine Mediated Vascular Adverse Effects|
|Study Start Date :||January 2011|
|Estimated Primary Completion Date :||October 2011|
|Estimated Study Completion Date :||September 2012|
No Intervention: Saline
Volunteers will receive an incremental rising dose infusion of IA NAC (6 doses) together with a co-infusion of normal saline to determine a dose response curve for arterial vasodilatation in the forearm.
Active Comparator: Histamine antagonists
Subjects will receive an increasing dose infusion of NAC as described in arm 1 but in this arm will receive a co-infusion of histamine antagonists (H1 and H2 antagonists) to determine vasodilatation in response to NAC in the presence of histamine antagonists.
Drug: Chlorphenamine and Ranitidine
We intend to use chlorphenamine (H1 antagonist) and ranitidine (H2 antagonist).Assuming NAC causes vasodilatation with an increase in forearm blood flow, we propose to administer 5 mcg/min to ensure maximal H1 blockade. In the presence of increased forearm blood flow, we propose to administer 37.5 mcg/min.
Active Comparator: Low dose paracetamol
Subjects will receive an increasing dose infusion of NAC as described in arm 1 but in this arm will receive a co-infusion of low dose paracetamol to determine whether the vasodilatory response to NAC is inhibited.
Therapeutic IV administration of 1g paracetamol results in a plasma concentration of ~12 mg/l. To achieve a desired concentration of ~25 mg/l, in the presence of a forearm blood blow of 50 ml/min, we would intend to administer an IA infusion of 1.25 mg/min. To account for the presence of increased forearm blood flow, we propose to administer 4 mg/min IA paracetamol.
Active Comparator: High dose paracetamol
Subjects will receive an increasing dose infusion of NAC as described in arm 1 but in this arm will receive a co-infusion of higher dose paracetamol to determine whether the vasodilatory response to NAC is inhibited.
To achieve a local paracetamol concentration of ~200 mg/l, a concentration comparable to potentially hepatotoxic concentrations following paracetamol overdose, we propose to administer 30 mg/min paracetamol.
- Attenuation of NAC induced vasodilatation by histamine antagonists (H1 and H2 antagonists) and/or paracetamol [ Time Frame: 10, 20, 30, 40, 50, 60, 70, 80, 90 minutes ]
- Inhibition of the inflammatory cascade contributes to a paracetamol mediated protective role against NAC adverse reactions. [ Time Frame: 10, 20, 30, 40, 50, 60, 70, 80, 90 minutes ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01209455
|Contact: Euan A Sandilands, MRCP BSc||+44 131 242 firstname.lastname@example.org|
|Clinical Research Facility, Royal Infirmary of Edinburgh||Recruiting|
|Edinburgh, Midlothian, United Kingdom, EH16 4SA|
|Principal Investigator: Euan A Sandilands, MRCP BSc|
|Principal Investigator:||Euan A Sandilands, MRCP BSc||NHS Lothian|