Central Nervous System Effects of DiphenhydraminePhase 4NCT05219604

Central Nervous System Effects Following Infusion of Diphenhydramine Using Pharmacokinetic and Pharmacodynamic Modeling

A Phase 4 study testing DiphenhydrAMINE Injectable Solution in people with Central Nervous System Effects of Diphenhydramine and Pharmacokinetics of Diphenhydramine, run by Dent Neuroscience Research Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study seeks to explore the magnitude and duration of central nervous system effects and pharmacokinetics after intravenous infusion of diphenhydramine. Read more about this study

Who is it for?: Ages 35 years and olderHealthy volunteers can take part
Conditions the study is for: Central Nervous System Effects of Diphenhydramine, Pharmacokinetics of Diphenhydramine
What is being tested?: DiphenhydrAMINE Injectable Solution
Type of treatment: Injection or infusion
How many people: 3 participants
Where: 1 siteUnited States
Study dates: 15 Mar 2022to 4 Oct 2022
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 35 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Medically-stable volunteers of either gender between 35 and 50 years old or over the age of 65
No medication changes anticipated for the duration of the study except as defined in protocol

Who cannot join

Insulin-dependent diabetes
Psychiatric or neurologic disease affecting cognition in a way that may interfere with study outcomes in the opinion of the investigator
Unstable Coronary Artery Disease (active angina, MI within 6 months, stent placement within 6 months, cardiac surgery within 6 months)
Estimated CrCl < 30 mL/min using the Cockroft-Gault equation based on ideal body weight or total body weight
Any malignancy actively being treated or not in remission
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

Show all 15Show fewer

Positive toxicology test for marijuana at screening visit or visit 2 or using marijuana not as defined in the protocol
Active or recent history of a substance use disorder within one year
Any medical condition that in the opinion of the investigator would disqualify the subject from participation in the study
Female subjects who are pregnant, planning to become pregnant, or breastfeeding on any study day
Female subjects of childbearing potential unwilling to use acceptable method of contraception during the study as defined in the protocol
Contraindication, known allergy, or suspected intolerability to study medication
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
Positive toxicology test for a drug that is inconsistent with permitted medication use (defined in the protocol) as interpreted by the investigator
Participation in any other investigational drug study during the study or within 4 weeks prior to screening

Trial locations and contacts

1 site in 1 country.

United States1 site

Dent Neurologic Institute
Amherst, New York, 14226

Other trials in United States

About this study

Official title: The Magnitude and Duration of the Central Nervous System Effects Following Intravenous Infusion of Diphenhydramine Using Pharmacokinetic and Pharmacodynamic Modeling

This study seeks to explore the magnitude and duration of central nervous system effects and pharmacokinetics after intravenous infusion of diphenhydramine.

Conditions: Central Nervous System Effects of Diphenhydramine, Pharmacokinetics of Diphenhydramine
Being tested: DiphenhydrAMINE Injectable Solution

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DiphenhydrAMINE Injectable SolutionDrug
Intravenous infusion of diphenhydramine 50 mg.

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Score of Battery of Cognitive Function Tests (Reaction Time)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Change in Score of Battery of Cognitive Function Tests (Digit Span)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Change in Score of Battery of Cognitive Function Tests (Visual Analog Scale for Sedation)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Change in Score of Battery of Cognitive Function Tests (Spatial Working Memory)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Change in Score of Battery of Cognitive Function Tests (Paired Associates Learning)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Change in Score of Battery of Cognitive Function Tests (Rapid Visual Information Processing)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)

Secondary outcomes (13)

Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Reaction Time)
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.
Measured: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Digit Span)
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.
Measured: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Visual Analog Scale for Sedation)
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.
Measured: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Spatial Working Memory)
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.
Measured: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Paired Associates Learning)
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.
Measured: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Rapid Visual Information Processing)
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.
Measured: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Diphenhydramine AUC
Difference between diphenhydramine pharmacokinetic area under the curve (AUC) in elderly subjects aged 65+ vs. adult subjects aged 35 to 50
Measured: Immediately after diphenhydramine administration to 480 minutes after diphenhydramine administration
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Reaction Time)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Digit Span)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Visual Analog Scale for Sedation)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Spatial Working Memory)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Paired Associates Learning)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Rapid Visual Information Processing)
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.
Measured: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Mar 20224 Oct 2022

First posted2 Feb 2022
Study start15 Mar 2022
Primary completion4 Oct 2022
Study completion4 Oct 2022

Why it stopped: Institution decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Central Nervous System Effects of DiphenhydramineStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05219604
Sponsor's protocol ID: DIP-PKPD
Status last verified: Jan 2026
First submitted: 18 Jan 2022
Last updated: 22 Jan 2026
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Magnitude and Duration of the Central Nervous System Effects Following Intravenous Infusion of Diphenhydramine Using Pharmacokinetic and Pharmacodynamic Modeling
ClinicalTrials.gov ID: NCT05219604
Acronym / sponsor ID: DIP-PKPD
Conditions: Central Nervous System Effects of Diphenhydramine, Pharmacokinetics of Diphenhydramine
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Institution decision
Enrolment: 3 participants (actual)
Lead sponsor: Dent Neuroscience Research CenterUniversity, hospital or other
Study start: 15 Mar 2022 (actual)
Primary completion: 4 Oct 2022 (actual)
Study completion: 4 Oct 2022 (actual)
First posted: 2 Feb 2022 (actual)
Results: Posted 22 Jan 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study seeks to explore the magnitude and duration of central nervous system effects and pharmacokinetics after intravenous infusion of diphenhydramine.

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 35 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Medically-stable volunteers of either gender between 35 and 50 years old or over the age of 65
No medication changes anticipated for the duration of the study except as defined in protocol

Key exclusion criteria (15 listed)

Insulin-dependent diabetes
Psychiatric or neurologic disease affecting cognition in a way that may interfere with study outcomes in the opinion of the investigator
Unstable Coronary Artery Disease (active angina, MI within 6 months, stent placement within 6 months, cardiac surgery within 6 months)
Estimated CrCl < 30 mL/min using the Cockroft-Gault equation based on ideal body weight or total body weight
Any malignancy actively being treated or not in remission

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DiphenhydrAMINE Injectable SolutionIntravenous infusion of diphenhydramine 50 mg.	Drug	–

Primary outcome

Change in Score of Battery of Cognitive Function Tests (Reaction Time)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.

13 secondary outcomes

Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Reaction Time)
Time frame: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Digit Span)
Time frame: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Visual Analog Scale for Sedation)
Time frame: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Spatial Working Memory)
Time frame: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Paired Associates Learning)
Time frame: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Score of Battery of Cognitive Function Tests at Specified Time Points (Rapid Visual Information Processing)
Time frame: Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)
Elderly vs. Adult Diphenhydramine AUC
Time frame: Immediately after diphenhydramine administration to 480 minutes after diphenhydramine administration
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Reaction Time)
Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Digit Span)
Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Visual Analog Scale for Sedation)
Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Spatial Working Memory)
Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Paired Associates Learning)
Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)
Elderly vs. Adult Change in Score of Battery of Cognitive Function Tests After Diphenhydramine (Rapid Visual Information Processing)
Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)

Results and safety

Results posted to the registry on 22 Jan 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Diphenhydramine 50 mg IV Infusion	3	3

Primary outcome: Change in Score of Battery of Cognitive Function Tests (Reaction Time)

Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine). Mean (Standard Deviation). Unit: ms

Measure	Diphenhydramine 50 mg IV Infusion n = 3
Reaction Time Pre-Diphenhydramine (Median Five-Choice Movement Time)	246 (51.4)
Reaction Time 30 Minutes Post-Diphenhydramine (Median Five-Choice Movement Time)	289.7 (87.8)
Reaction Time 210 Minutes Post-Diphenhydramine (Median Five-Choice Movement Time)	267.0 (72.9)
Reaction Time 450 Minutes Post-Diphenhydramine (Median Five-Choice Movement Time)	292.8 (94.6)

Population analysed: Data were collected for 3 study participants prior to study termination. There were no participants with data collected at the following time points due to early study termination as no participants were enrolled in the group to have data collected at these time points: 60 min, 240 min, or 480 min post-diphenhydramine. Data were not analyzed via ANOVA with contrast or via PK/PD modeling as planned as there were lack of sufficient data to perform this analysis due to early study termination.

Primary outcome: Change in Score of Battery of Cognitive Function Tests (Digit Span)

Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine). Mean (Standard Deviation). Unit: units on a scale

Measure	Diphenhydramine 50 mg IV Infusion n = 3
Digit Span Pre-Diphenhydramine (Maximum Span Passed Forwards)	5 (1.0)
Digit Span 30 Minutes Post-Diphenhydramine (Maximum Span Passed Forwards)	5.3 (1.5)
Digit Span 210 Minutes Post-Diphenhydramine (Maximum Span Passed Forwards)	6.3 (1.2)
Digit Span 450 Minutes Post-Diphenhydramine (Maximum Span Passed Forwards)	5.7 (1.2)

Primary outcome: Change in Score of Battery of Cognitive Function Tests (Visual Analog Scale for Sedation)

Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine). Mean (Standard Deviation). Unit: units on a scale

Measure	Diphenhydramine 50 mg IV Infusion n = 3
Visual Analog Scale for Sedation Pre-Diphenhydramine	12.3 (0.4)
Visual Analog Scale for Sedation 30 Minutes Post-Diphenhydramine	4.9 (5.3)
Visual Analog Scale for Sedation 210 Minutes Post-Diphenhydramine	7.9 (3.7)
Visual Analog Scale for Sedation 450 Minutes Post-Diphenhydramine	6.9 (5.9)

Primary outcome: Change in Score of Battery of Cognitive Function Tests (Spatial Working Memory)

Time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine). Mean (Standard Deviation). Unit: units on a scale

Measure	Diphenhydramine 50 mg IV Infusion n = 3
Spatial Working Memory Pre-Diphenhydramine (Between Errors)	1.7 (2.9)
Spatial Working Memory 30 Minutes Post-Diphenhydramine (Between Errors)	4.0 (6.9)
Spatial Working Memory 210 Minutes Post-Diphenhydramine (Between Errors)	1.0 (1.7)
Spatial Working Memory 450 Minutes Post-Diphenhydramine (Between Errors)	2.3 (4.0)

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: 21 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Diphenhydramine 50 mg IV Infusion	0 of 3 (0%)	0 of 3 (0%)	0 of 3

Limitations and caveats (from the sponsor): The study was terminated due to institution decision prior to data analysis.

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Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michelle Rainka, PharmD principal investigator

Dent Neurologic Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Score of Battery of Cognitive Function Tests (Reaction Time) (time frame: Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05219604.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026; AzTrials last refreshed its copy on 7 Nov 2026.