Sex-related Differences in the Response to the Muscle Relaxant Drug Mivacurium

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. Identifier: NCT01906528
Recruitment Status : Completed
First Posted : July 24, 2013
Last Update Posted : April 11, 2014
Oslo University Hospital
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
Muscle relaxants are drugs providing muscle relaxation during surgical treatment. Previous studies have shown that males and females respond differently to this kind of drug. Our hypothesis is that males are more sensitive to the effect of Mivacurium (a muscle relaxant) than females, meaning that males need a lower blood concentration of the drug than females in order to obtain a given effect.

Condition or disease Intervention/treatment Phase
Muscle Relaxation Sex Drug: Mivacurium Phase 1

Detailed Description:
Muscle relaxants are a type of drug used to provide muscle relaxation during induction of anesthesia and surgical treatment. Residual drug effect postoperatively (i.e. residual muscle relaxation) occurs frequently and studies have shown that this may be harmful in certain groups of patients. Of special concern is residual effect on upper airway and breathing muscles. A previous study has shown that males and females respond differently to the effect of this kind of drug. It appears that some muscle groups which are important for airway protection and breathing are more sensitive to the effect of muscle relaxants in males than females. Males may therefore be more susceptible to postoperative lung complications than females. In this study we try to determine what causes the observed sex-related difference in response to the muscle relaxant Mivacurium. We have previously shown that this sex-related difference cannot be explained by different pharmacokinetics (what the body does to the drug) in males and females. Our hypothesis is that a pharmacodynamic (what the drug does to the body) difference between sexes exists, i.e. that a lower blood concentration of Mivacurium is needed in males than females in order to obtain a predefined degree of muscle relaxation in certain muscle groups.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Pharmacodynamics of Mivacurium in Males and Females: A Study in Human Volunteers
Study Start Date : March 2013
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Males vs females
Constant-rate IV infusions of Mivacurium, range 1.0 - 3 micro/kg/min, duration 150 - 180 min
Drug: Mivacurium
Effect of Mivacurium in males vs females
Other Name: Mivacron

Primary Outcome Measures :
  1. Pharmacodynamics of Mivacurium [ Time Frame: 6 months ]
    The mivacurium drug concentration in the blood associated with 50% of maximal drug effect at steady-state conditions (Css50) will be determined at the thumb and the handgrip muscles.

Secondary Outcome Measures :
  1. Clearance of Mivacurium [ Time Frame: 6 months ]
    Clearance calculated as the relationship between steady-state infusion rate of Mivacurium and Mivacurium blood concentration.

Other Outcome Measures:
  1. Relationship between thumb acceleration (TOF ratio) and handgrip strength in both sexes [ Time Frame: 6 months ]
    Thumb acceleration secondary to nerve stimulation at the ulnar nerve (TOF ratio) is an objective way of monitoring the effect of muscle relaxants that is used frequently during clinical anesthesia. Handgrip strength will be monitored with a dynamometer.

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria: Healthy individuals with no current medication -

Exclusion Criteria: Previous complications during anesthesia, pregnancy, allergy to muscle relaxants, smoking, gastrointestinal reflux.

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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 identifier (NCT number): NCT01906528

United States, California
University of California, UCSF
San Francisco, California, United States, 94131
Sponsors and Collaborators
University of California, San Francisco
Oslo University Hospital
Principal Investigator: John R Feiner, MD University of California, UCSF, San Francisco, USA

Responsible Party: University of California, San Francisco Identifier: NCT01906528     History of Changes
Other Study ID Numbers: IRB11-07970
First Posted: July 24, 2013    Key Record Dates
Last Update Posted: April 11, 2014
Last Verified: April 2014

Keywords provided by University of California, San Francisco:
Nondepolarizing neuromuscular blocking drug

Additional relevant MeSH terms:
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs