Mechanisms of N-acetylcysteine Mediated Vascular Adverse Effects
|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|
Show Detailed Description
|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 ]
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|