Central Nervous System Effects of Diphenhydramine, Pharmacokinetics of Diphenhydramine
Conditions
Brief summary
This study seeks to explore the magnitude and duration of central nervous system effects and pharmacokinetics after intravenous infusion of diphenhydramine.
Interventions
DRUGDiphenhydrAMINE Injectable Solution
Intravenous infusion of diphenhydramine 50 mg.
Sponsors
Dent Neuroscience Research Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Medically-stable volunteers of either gender between 35 and 50 years old or over the age of 65 2. No medication changes anticipated for the duration of the study except as defined in protocol
Exclusion criteria
1. Insulin-dependent diabetes 2. Psychiatric or neurologic disease affecting cognition in a way that may interfere with study outcomes in the opinion of the investigator 3. Unstable Coronary Artery Disease (active angina, MI within 6 months, stent placement within 6 months, cardiac surgery within 6 months) 4. Estimated CrCl \< 30 mL/min using the Cockroft-Gault equation based on ideal body weight or total body weight 5. Any malignancy actively being treated or not in remission 6. Currently taking any CNS stimulant or depressant medications that may interfere with study outcomes in the opinion of the investigator unless using as defined in the protocol 7. Positive toxicology test for marijuana at screening visit or visit 2 or using marijuana not as defined in the protocol 8. Active or recent history of a substance use disorder within one year 9. Any medical condition that in the opinion of the investigator would disqualify the subject from participation in the study 10. Female subjects who are pregnant, planning to become pregnant, or breastfeeding on any study day 11. Female subjects of childbearing potential unwilling to use acceptable method of contraception during the study as defined in the protocol 12. Contraindication, known allergy, or suspected intolerability to study medication 13. Receipt of an antihistamine within 5 half-lives prior to the start of study visit 1 or study visit 2, as determined by the investigator 14. Positive toxicology test for a drug that is inconsistent with permitted medication use (defined in the protocol) as interpreted by the investigator 15. Participation in any other investigational drug study during the study or within 4 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Score of Battery of Cognitive Function Tests (Reaction Time) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the results of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation after diphenhydramine administration compared to baseline. Reaction Time Median Five-Choice Reaction Time is the median duration it took for a subject to release the response button after the presentation of the target stimulus, calculated across correct, assessed trials in which the stimulus could appear in any one of five locations. Lower is better. Minimum score is 100 and maximum score is 5100. |
| Change in Score of Battery of Cognitive Function Tests (Digit Span) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the results of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation after diphenhydramine administration compared to baseline. Digit Span Maximum Span Passed Forwards is the longest sequence problem successfully reached and passed by the subject. Higher is better. Minimum score is 0 and maximum score is 9. |
| Change in Score of Battery of Cognitive Function Tests (Visual Analog Scale for Sedation) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the results of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation after diphenhydramine administration compared to baseline. The Visual Analog Scale for Sedation is a scale where participants indicate their current state on a scale from "Sedated" to "Alert". Higher score is more alert. Minimum score is 0 and maximum score is 12.8. |
| Change in Score of Battery of Cognitive Function Tests (Spatial Working Memory) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the results of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation after diphenhydramine administration compared to baseline. Spatial Working Memory Between Errors is the number of times the subject incorrectly revisits a box in which a token has been previously found. Lower is better. Minimum score is 0 and maximum score is 63. |
| Change in Score of Battery of Cognitive Function Tests (Paired Associates Learning) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the results of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation after diphenhydramine administration compared to baseline. Paired Associates Learning First Attempt Memory Score is the number of times a subject chose the correct box on their first attempt when recalling the pattern locations. Higher is better. Minimum score is 0 and maximum score is 20. |
| Change in Score of Battery of Cognitive Function Tests (Rapid Visual Information Processing) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the results of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation after diphenhydramine administration compared to baseline. Rapid Visual Processing Median Response Latency is the median response latency on trials where the subject responded correctly, calculated across all assessed trials. Lower is better. Minimum score is 0 and maximum score is 908. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Reaction Time) | Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | Score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (0, 30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration). Reaction Time Median Five-Choice Reaction Time is the median duration it took for a subject to release the response button after the presentation of the target stimulus, calculated across correct, assessed trials in which the stimulus could appear in any one of five locations. Lower is better. Minimum score is 100 and maximum score is 5100. |
| Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Digit Span) | Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | Score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (0, 30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration). Digit Span Maximum Span Passed Forwards is the longest sequence problem successfully reached and passed by the subject. Higher is better. Minimum score is 0 and maximum score is 9. |
| Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Visual Analog Scale for Sedation) | Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | Score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (0, 30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration). The Visual Analog Scale for Sedation is a scale where participants indicate their current state on a scale from "Sedated" to "Alert". Higher score is more alert. Minimum score is 0 and maximum score is 12.8. |
| Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Spatial Working Memory) | Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | Score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (0, 30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration). Spatial Working Memory Between Errors is the number of times the subject incorrectly revisits a box in which a token has been previously found. Lower is better. Minimum score is 0 and maximum score is 63. |
| Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Paired Associates Learning) | Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | Score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (0, 30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration). Paired Associates Learning First Attempt Memory Score is the number of times a subject chose the correct box on their first attempt when recalling the pattern locations. Higher is better. Minimum score is 0 and maximum score is 20. |
| Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Rapid Visual Information Processing) | Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | Score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (0, 30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration). Rapid Visual Processing Median Response Latency is the median response latency on trials where the subject responded correctly, calculated across all assessed trials. Lower is better. Minimum score is 0 and maximum score is 908. |
| Elderly vs. Adult Diphenhydramine AUC | Immediately after diphenhydramine administration to 480 minutes after diphenhydramine administration | Difference between diphenhydramine pharmacokinetic area under the curve (AUC) in elderly subjects aged 65+ vs. adult subjects aged 35 to 50 |
| Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Reaction Time) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) compared to baseline. Reaction Time Median Five-Choice Reaction Time is the median duration it took for a subject to release the response button after the presentation of the target stimulus, calculated across correct, assessed trials in which the stimulus could appear in any one of five locations. Lower is better. Minimum score is 100 and maximum score is 5100. |
| Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Digit Span) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) compared to baseline. Digit Span Maximum Span Passed Forwards is the longest sequence problem successfully reached and passed by the subject. Higher is better. Minimum score is 0 and maximum score is 9. |
| Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Visual Analog Scale for Sedation) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) compared to baseline. The Visual Analog Scale for Sedation is a scale where participants indicate their current state on a scale from "Sedated" to "Alert". Higher score is more alert. Minimum score is 0 and maximum score is 12.8. |
| Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Spatial Working Memory) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) compared to baseline. Spatial Working Memory Between Errors is the number of times the subject incorrectly revisits a box in which a token has been previously found. Lower is better. Minimum score is 0 and maximum score is 63. |
| Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Paired Associates Learning) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) compared to baseline. Paired Associates Learning First Attempt Memory Score is the number of times a subject chose the correct box on their first attempt when recalling the pattern locations. Higher is better. Minimum score is 0 and maximum score is 20. |
| Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Rapid Visual Information Processing) | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | Change in the score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) compared to baseline. Rapid Visual Processing Median Response Latency is the median response latency on trials where the subject responded correctly, calculated across all assessed trials. Lower is better. Minimum score is 0 and maximum score is 908. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichelle Rainka, PharmD
Dent Neurologic Institute
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
None listed