Evaluation of Three Potential Central Nervous System (CNS) Pretreatments for Soman Exposure on Human Performance

Evaluation of Three Potential CNS Pretreatments for Soman Exposure - Huperzine A, Donepezil, and Galantamine - on Human Performance

The primary objective of this study is to determine whether huperzine A, donepezil, and galantamine impact militarily relevant aspects of neurocognitive performance in humans, compared to placebo.

Study Overview

• Status: Completed
• Conditions: Biomarkers, Pharmacological
• Intervention / Treatment: Drug: Huperzine A; Drug: Donepezil; Drug: Galantamine; Other: Placebo

Detailed Description

The primary objective of this study is to determine whether huperzine A, donepezil, and galantamine impact militarily relevant aspects of neurocognitive performance in humans, compared to placebo.

Secondary: Secondary objectives are to correlate neurocognitive performance effects with degree of inhibition and therefore sequestration of red blood cell AChE by huperzine A, donepezil, and galantamine, and to monitor the safety of the study drugs in healthy adult (18-39 years) males and females.

In a double-blind, randomized, placebo-controlled, parallel-groups design, normal, healthy, adult male and female volunteers will be administered one of the drug/doses. They will be tested prior to and periodically for militarily relevant performance tasks for up to 8 hours post-dose and for cholinesterase levels via finger prick.

• Study Type: Observational
• Enrollment (Actual): 84

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Institute of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Healthy adults (18-39 years) males and females, military or civilian

Description

Inclusion Criteria:

• All healthy men and women 18 to 39 years of age are eligible to participate.

Exclusion Criteria:

Must be able to swallow whole pills.

• Self-reported habitual nightly sleep amounts outside the target range of 6-8 hours (i.e., less than 6 hours per night or more than 8 hours per night, on average)
• Cardiovascular disease (to include but not limited to arrhythmias, valvular heart disease, congestive heart failure, family history of sudden cardiac death or myocardial infarction) as determined by participant self report.
• Current hypertension or high blood pressure (greater than 140/90)
• Neurologic disorder (to include but not limited to epilepsy or another seizure disorder, amnesia for any reason, hydrocephalus, MS, narcolepsy or other sleep disorders)
• Kidney disease
• History of psychiatric disorder requiring hospitalization or psychiatric medication for any length of time
• Beck Depression Inventory score of 14 or above
• Underlying pulmonary disease requiring daily inhaler use
• Regular nicotine use (or addiction) (defined as more than 1 cigarette or equivalent per week) within the last 3 years
• Heavy alcohol use (more than 2 drinks per day; http://www.cdc.gov/alcohol/faqs.htm#10)
• Use of other illicit drugs (to include but not limited to benzodiazepines, amphetamines, cocaine, marijuana)
• Known liver disease or liver abnormalities as determined by a laboratory test
• Known ulcer disease or risk of ulcer disease (stomach bleeding)
• Self-reported history of caffeine use in excess of 400 mg (8 caffeinated sodas or 3-4 cups, each ~ 6 oz, of coffee) per day on average
• Pregnancy (females)
• Breast-feeding (females)
• Prior anaphylactic reaction, angioedema, or other severe psychological reactions to any of the test compounds

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Placebo	Other: Placebo; dosage form: tablet dosage frequency: once only
Huperzine A: 100 ug	Drug: Huperzine A; dosage form: tablet dose frequency: once only
Huperzine A: 200 ug	Drug: Huperzine A; dosage form: tablet dose frequency: once only
Donepezil: 2.5 mg	Drug: Donepezil; dosage form: tablet dosage frequency: once only
Donepezil: 5 mg	Drug: Donepezil; dosage form: tablet dosage frequency: once only
Galantamine: 4 mg	Drug: Galantamine; dosage form: tablet dosage frequency: once only
Galantamine: 8 mg	Drug: Galantamine; dosage form: tablet dosage frequency: once only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observe military relevant neurocognitive performance in humans taking huperzine A, donepezil and galantamine compared to placebo.	The primary objective of this study is to determine whether huperzine A (a nutraceutical), donepezil (Aricept®), and galantamine (Razadyne®), impact militarily relevant aspects of neurocognitive performance in humans, compared to placebo.	6pm Day 1 to 7pm Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlate neurocognitive performance effects of huperzine A, donepezil and galantamine and to monitor the safety of the study drugs in healthy adults.	Secondary objectives are to correlate neurocognitive performance effects with degree of sequestration of red blood cell AChE by huperzine A, donepezil, and galantamine, and to monitor the safety of the study drugs in healthy adults.	6pm Day 1 to 7pm Day 2

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: Walter Reed Army Institute of Research (WRAIR)
• Investigators: Principal Investigator: MAJ James E Moon, MC, Walter Reed Army Institute of Research (WRAIR)

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: August 31, 2010
• First Submitted That Met QC Criteria: September 2, 2010
• First Posted (Estimate): September 3, 2010

Study Record Updates

• Last Update Posted (Actual): May 3, 2017
• Last Update Submitted That Met QC Criteria: May 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Central nervous system; Cholinesterase; Neurocognitive performance testing
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Nootropic Agents; Cholinesterase Inhibitors; Parasympathomimetics; Donepezil; Huperzine A; Galantamine
• Other Study ID Numbers: WRAIR 1650; A-16072 (Other Identifier: HSRRB)