Analysis of Atropine and Propranolol Induced Changes - Full Text View

Sponsor:	National Institute on Aging (NIA)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00251602

Purpose

The purpose of this study is to learn the effects of genetic make up on response to the drugs atropine and propranolol, to examine how changes in heart rate and blood pressure can be measured, and to test a new statistical analysis method.

Condition	Intervention	Phase
Healthy	Drug: Atropine Drug: Propranolol Drug: Normal Saline	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Wavelet Transform and Pharmacodynamic Analysis of Atropine and Propranolol Induced Changes in Human Heart Rate Variability

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

Drug Information available for: Atropine Propranolol hydrochloride Propranolol Dexpropranolol Atropine sulfate

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Changes in heart rate and blood pressure [ Time Frame: every 2 minutes during drug infusions and every 10 minutes during the remainder of the study time ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	March 2003
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 II ACE genotype	Drug: Atropine One-time 10 mcg/kg infusion over 30 minutes, followed by a 10 mcg/kg bolus Drug: Propranolol One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline
Experimental: 2 ID ACE genotype	Drug: Atropine One-time 10 mcg/kg infusion over 30 minutes, followed by a 10 mcg/kg bolus Drug: Propranolol One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline
Experimental: 3 DD ACE genotype	Drug: Atropine One-time 10 mcg/kg infusion over 30 minutes, followed by a 10 mcg/kg bolus Drug: Propranolol One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline
Placebo Comparator: 4 II ACE genotype	Drug: Propranolol One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline Drug: Normal Saline One-time 0.25 ml/min infusion over 30 minutes Other Name: NS
Placebo Comparator: 5 ID ACE genotype	Drug: Propranolol One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline Drug: Normal Saline One-time 0.25 ml/min infusion over 30 minutes Other Name: NS
Placebo Comparator: 6 DD ACE genotype	Drug: Propranolol One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline Drug: Normal Saline One-time 0.25 ml/min infusion over 30 minutes Other Name: NS

Detailed Description:

Healthy volunteers will be recruited and screened for eligibility. Participants will be placed into three possible groups based on genetic information obtained during screening. Rolling admissions will continue until at least 10 participants have been recruited for each genetic group. Participants will be randomly assigned to receive either the control (propranolol and saline) or combined drug (propranolol and atropine) treatment in a non-blinded fashion. The participant will return over one week later to receive the alternate treatment. Continuous heart rate/blood pressure data will be recorded until the end of the study period. Respiratory rate will be maintained at a fixed rate. Participants will undergo an orthostasis task, receive the drug or control infusions, and blood samples will then be obtained to determine drug concentrations at specific time intervals. Several relatively new mathematical techniques will be applied to the data.

Eligibility

Ages Eligible for Study:	21 Years to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy male and female volunteers
Ages 21-40
Body Mass Index >18.0 and <27.0

Exclusion Criteria:

History of any chronic illnesses including cardiac diseases and bleeding problems
Drug use of any kind
Participation in any clinical trial within the last month
Tobacco use and/or alcohol abuse
Use of dietary supplements and unwillingness to refrain

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00251602

Locations

United States, Maryland
National Institute on Aging, Harbor Hospital
Baltimore, Maryland, United States, 21225

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Shari M. Ling, MD

National Institute on Aging, Clinical Research Branch

More Information

Publications:

Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981 Jul 10;213(4504):220-2.

Craft N, Schwartz JB. Effects of age on intrinsic heart rate, heart rate variability, and AV conduction in healthy humans. Am J Physiol. 1995 Apr;268(4 Pt 2):H1441-52.

Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell'Orto S, Piccaluga E, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986 Aug;59(2):178-93.

Responsible Party:	Shari Ling, M.D., National Institute on Aging
ClinicalTrials.gov Identifier:	NCT00251602 History of Changes
Other Study ID Numbers:	AG0059
Study First Received:	November 8, 2005
Last Updated:	April 21, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

heart rate variability
gene response

Additional relevant MeSH terms:

Atropine
Propranolol
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents

Respiratory System Agents
Mydriatics
Parasympatholytics
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on February 12, 2012