Analysis of Atropine and Propranolol Induced Changes

Wavelet Transform and Pharmacodynamic Analysis of Atropine and Propranolol Induced Changes in Human Heart Rate Variability

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Atropine; Drug: Propranolol; Drug: Normal Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: NS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in heart rate and blood pressure	every 2 minutes during drug infusions and every 10 minutes during the remainder of the study time

Collaborators and Investigators

• Sponsor: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Shari M. Ling, MD, National Institute on Aging, Clinical Research Branch

Publications and helpful links

General Publications

• 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. doi: 10.1161/01.res.59.2.178.
• 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. doi: 10.1126/science.6166045.
• 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. doi: 10.1152/ajpheart.1995.268.4.H1441.

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: November 8, 2005
• First Submitted That Met QC Criteria: November 8, 2005
• First Posted (Estimate): November 10, 2005

Study Record Updates

• Last Update Posted (Estimate): August 6, 2012
• Last Update Submitted That Met QC Criteria: August 3, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: heart rate variability; gene response
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Propranolol; Atropine
• Other Study ID Numbers: AG0059