Single-dose Novel Selective alpha2c Antagonist Pharmaco-MRI Study in Healthy Volunteers (SNAP_MRI)

The Effects of Single-dose Administration of a Novel Selective alpha2c Antagonist on Emotional and Cognitive Processing in Healthy Volunteers: an fMRI Investigation

The aim of the present study is to investigate changes in neural activity (BOLD signal), as measured using fMRI, in brain areas associated with emotional and working memory during task performance after single-dose administration of a novel selective alpha2c adrenoceptor antagonist (ORM-12741) in healthy volunteers. Further, it will be explored whether ORM-12741 affects connectivity between brain areas in rest, as measured using fMRI, and cognitive performance in the sample under investigation.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: ORM-12741; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • UCT Dept. Psychiatry & Mental Health / CUBIC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• good command of English language
• right handedness
• normal or corrected-to-normal vision

Exclusion Criteria:

• personal history or active presence of psychiatric conditions
• usage of psychotropic medication within the past 3 months
• pregnancy or breast-feeding status
• systolic blood pressure < 90 mmHg or > 140 mmHg at screening visit
• diastolic blood pressure < 50 mmHg or > 90 mmHg at screening visit
• resting heart rate < 45 beats/minute or > 100 beats/minute at screening visit
• active presence of medical condition at physical examination
• history of major traumatic brain injury
• any other contraindication to MRI of the brain
• use of psychoactive substances incl. alcohol in 24 hours prior to test session

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dosage (60mg) ORM-12741; 6 x 10 mg ORM-12741 immediate release capsules in a single dose	Drug: ORM-12741; Novel selective alpha2c adrenoceptor antagonist
Experimental: Low-dosage (10mg) ORM-12741; 1 x 10 mg ORM-12741 immediate release capsules and 5 x placebo capsules in a single dose	Drug: ORM-12741; Novel selective alpha2c adrenoceptor antagonist
Placebo Comparator: Placebo; 6 x placebo capsules in a single dose	Drug: Placebo; Identical in appearance to experimental drug, not psycho-active

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of ORM-12741 on BOLD signal in fMRI of the brain areas associated with emotional memory	1-1.5 hours post medication intake
Effect of ORM-12741 on BOLD signal in fMRI of the brain areas associated with working memory	1-1.5 hours post medication intake

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of ORM-12741 on connectivity measures between brain areas as measured with BOLD signal in fMRI obtained in a resting state	1.5-2 hours post medication intake
Effect of ORM-12741 on memory task performance (as measured by accuracy and response latency)	1-3 hours post medication intake

Collaborators and Investigators

• Sponsor: University of Cape Town
• Collaborators: University of Oxford; Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Dan J. Stein, MD, PhD, University of Cape Town

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): December 6, 2018

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 13, 2018
• First Posted (Actual): February 20, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Physiological Effects of Drugs; Mood disorders; Behavioral Symptoms; Noradrenalin Agents
• Other Study ID Numbers: 069/2017; N2/19/8/2 (Other Identifier: MCC South Africa); DOH-27-0218-5843 (Registry Identifier: SANCTR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No