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

NCT05219604 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: DIP-PKPD
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pharmacokinetics of Diphenhydramine; Central Nervous System Effects of Diphenhydramine

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  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)

  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)

  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)

  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)

  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)

  Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration)

Interventions

DiphenhydrAMINE Injectable Solution DRUG

Intravenous infusion of diphenhydramine 50 mg.

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Dent Neuroscience Research Center: lead

Study Sites (1)

Dent Neurologic Institute

Amherst, New York, 14226, United States

Location

Limitations and Caveats

The study was terminated due to institution decision prior to data analysis.

Results Point of Contact

• Title: Michelle Rainka, PharmD
• Organization: Dent Neurologic Institute

mrainka@dentinstitute.com

716-250-2000

Study Officials

• Michelle Rainka, PharmD

  Dent Neurologic Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 2, 2022
• Study Start: March 15, 2022
• Primary Completion: October 4, 2022
• Study Completion: October 4, 2022
• Last Updated: January 22, 2026
• Results First Posted: January 22, 2026

Record last verified: 2026-01

Locations

US (1)