Analysis of Atropine and Propranolol Induced Changes
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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:
|
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- Changes in heart rate and blood pressure [every 2 minutes during drug infusions and every 10 minutes during the remainder of the study time]
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.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.
- AG0059