Characterizing and Predicting Drug Effects on Cognition

NCT01889602 | Completed Phase 4 Results DMC

• 1 other identifier: CPDEC
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive impairment is a widely reported side effect of many commonly used drugs. Even a mild, untoward effect on an essential function such a linguistic behavior, a directly observable product of complex cognitive processes, is disruptive to daily life. Nevertheless, the mechanisms underlying a drug's impact on cognition are poorly understood. This lack of understanding impedes the ability to predict both the effects of drugs in development and the degree to which an individual is vulnerable to the cognitive impact of a particular agent. Topiramate (TPM, an antiepileptic drug) is, with increasing frequency, being prescribed for a range of conditions including migraine prophylaxis, obesity and pain. It is a prime example of a drug that causes speech and language problems severe enough in some patients to result in discontinuation of therapy. For reasons not well understood, TPM has a poorer cognitive profile than many of the older antiepileptic drugs. The investigators' rational for this study is that it will offer insight into the mechanisms underlying drug-induced cognitive deficits.

Conditions

Cognitive Deficits

Keywords

Healthy volunteers; Topiramate; Neurocognition; Drug-induced cognitive deficits

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in COWA Unique Word Count

  Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.

  Session 1 to Session 5

• Change From Baseline in Spontaneous Narrative Raw Word Count

  Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.

  Session 1 to Session 5

Study Arms (3)

Topiramate 100mg

EXPERIMENTAL

Participant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 100mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments.

Drug: Lorazepam; Other: Placebo; Drug: Topiramate 100mg

Topiramate 150mg

EXPERIMENTAL

Participant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 150mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments.

Drug: Lorazepam; Other: Placebo; Drug: Topiramate 150mg

Topiramate 200mg

EXPERIMENTAL

Participant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 200mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments.

Drug: Lorazepam; Other: Placebo; Drug: Topiramate 200mg

Interventions

Lorazepam DRUG

Lorazepam: 2mg, po, 1x

Also known as: Ativan

Topiramate 100mg; Topiramate 150mg; Topiramate 200mg

Placebo OTHER

Non-active placebo, po, 1x

Topiramate 100mg; Topiramate 150mg; Topiramate 200mg

Topiramate 100mg DRUG

Topiramate: 100 mg, po, 1x

Also known as: Topamax

Topiramate 100mg

Topiramate 150mg DRUG

Topiramate: 150 mg, po, 1x

Also known as: Topamax

Topiramate 150mg

Topiramate 200mg DRUG

Topiramate: 200 mg, po, 1x

Also known as: Topamax

Topiramate 200mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men and women
• Ages 18-50
• Women are post-menopausal or using approved birth control methods
• To control for brain lateralization of language functions, subjects need to have a dominant right hand.

You may not qualify if:

• Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, renal, neurologic, and/or psychiatric disease including suicidality
• Vision or hearing impairments
• Current or a history of drug or alcohol abuse
• living outside of the Twin Cities Metropolitan area.
• The use of concomitant medications known to affect Topiramate (TPM), Lorazepam (LZP), or the use of any concomitant medications that may alter cognitive function
• Prior adverse reaction or prior hypersensitivity to TPM, LZP or related compounds
• A positive pregnancy test (administered to all women before enrollment, and prior to each study session).
• Subjects who have received any investigational drug within the previous 30 days

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Related Publications (1)

• Callisto SP, Illamola SM, Birnbaum AK, Barkley CM, Bathena SPR, Leppik IE, Marino SE. Severity of Topiramate-Related Working Memory Impairment Is Modulated by Plasma Concentration and Working Memory Capacity. J Clin Pharmacol. 2020 Sep;60(9):1166-1176. doi: 10.1002/jcph.1611. Epub 2020 Apr 16.

  PMID: 32297992 DERIVED

MeSH Terms

Conditions

Cognition Disorders

Interventions

Lorazepam; Topiramate

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Dr. Susan Marino
• Organization: University of Minnesota

marin007@umn.edu

612-624-2964

Study Officials

• Susan E. Marino, PhD

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2013
• First Posted: June 28, 2013
• Study Start: July 1, 2013
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: December 17, 2019
• Results First Posted: December 17, 2019

Record last verified: 2019-12

Locations

US (1)