Analysis of Atropine and Propranolol Induced Changes

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Atropine
* Drug: Propranolol
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>II ACE genotype | Drug: Atropine<br>* One-time 10 mcg/kg infusion over 30 minutes, followed by a 10 mcg/kg bolus<br>Drug: Propranolol<br>* One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline<br>|
| Experimental: 2<br>ID ACE genotype | Drug: Atropine<br>* One-time 10 mcg/kg infusion over 30 minutes, followed by a 10 mcg/kg bolus<br>Drug: Propranolol<br>* One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline<br>|
| Experimental: 3<br>DD ACE genotype | Drug: Atropine<br>* One-time 10 mcg/kg infusion over 30 minutes, followed by a 10 mcg/kg bolus<br>Drug: Propranolol<br>* One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline<br>|
| Placebo Comparator: 4<br>II ACE genotype | Drug: Propranolol<br>* One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline<br>Drug: Normal Saline<br>* One-time 0.25 ml/min infusion over 30 minutes<br>* Other names: NS;|
| Placebo Comparator: 5<br>ID ACE genotype | Drug: Propranolol<br>* One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline<br>Drug: Normal Saline<br>* One-time 0.25 ml/min infusion over 30 minutes<br>* Other names: NS;|
| Placebo Comparator: 6<br>DD ACE genotype | Drug: Propranolol<br>* One-time 0.8mg/kg/hr infusion (maximum dose not to exceed 20mg) over 20 minutes, followed by either atropine or normal saline<br>Drug: Normal Saline<br>* One-time 0.25 ml/min infusion over 30 minutes<br>* Other names: NS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart rate variability, gene response