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Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a (FASTMAS_Kor2)

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ClinicalTrials.gov Identifier: NCT02218736
Recruitment Status : Completed
First Posted : August 18, 2014
Last Update Posted : March 26, 2018
Sponsor:
Collaborators:
Yale University
Baylor College of Medicine
Indiana University
Icahn School of Medicine at Mount Sinai
Case Western Reserve University
Information provided by (Responsible Party):
Duke University

Brief Summary:
The available treatment for patients with mood and anxiety disorders have significant limitations (Rush, 2007; Denys and de Geus, 2005). There is a need to develop new treatments for people with these disorders. Many research studies carried out in animals and a few preliminary studies carried out in humans suggest that medications which block kappa opioid receptors (KOR) have potential for being effective new treatments for patients with mood and anxiety spectrum disorders. These medications have shown particular promise for improving one important type of difficulty experienced by many patients who suffer from mood and anxiety spectrum disorders referred to as anhedonia, which is an impairment in reward-related function. In this study we will test the hypothesis that KOR antagonism is a promising means of improving anhedonia in patients with mood and anxiety spectrum disorders. We will do so by evaluating whether we can establish Proof of Concept (POC) that a relatively selective KOR antagonist, CERC-501 (formerly known as LY2456302), engages neural circuits involved in mediating reward-related function in patients with mood and anxiety spectrum disorders with anhedonia. We are attempting to establish POC in this study in order to determine whether there is a sufficient basis for pursuing future work evaluating whether KOR antagonism has therapeutic effects on clinical and behavioral measures of reward-related functioning.

Condition or disease Intervention/treatment Phase
ANXIETY DISORDERS (or Anxiety and Phobic Neuroses) Drug: CERC-501 Drug: placebo Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 89 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: A Phase 2a Study to Evaluate the Kappa Opioid Receptor As a Target for the Treatment of Mood and Anxiety Spectrum Disorders by Evaluation of Whether CERC-501 Engages Key Neural Circuitry Related to the Hedonic Response
Actual Study Start Date : June 2015
Actual Primary Completion Date : November 1, 2017
Actual Study Completion Date : December 1, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: CERC-501
Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks
Drug: CERC-501
Oral dosing of 10 mg CERC-501 daily for 8 weeks
Other Name: Kappa Opioid Receptor Antagonist; LY2456302

Placebo Comparator: Placebo
Oral daily administration of 10 mg placebo for 8 weeks
Drug: placebo
oral dosing of 10 mg placebo daily for 8 weeks




Primary Outcome Measures :
  1. Functional MRI evaluation of task-related ventral striatal activation occurring with reward and anticipation during the Monetary Incentive Delay Task [ Time Frame: Week 8 ]
    Establish POC for KOR antagonism by evaluating the impact of CERC-501 relative to Placebo on reward-related neural circuitry in terms of ventral striatal activation during anticipation of reward during the Monetary Incentive Delay Task. Evaluation by fMRI after 8 weeks of daily drug dosing.


Secondary Outcome Measures :
  1. Clinical Anhedonia measured by the Snaith-Hamilton Pleasure Scale (SHAPS; total score) [ Time Frame: 8 weeks ]
    To determine if CERC-501 is superior to placebo in improving a clinical self-report measure of anhedonia using the Snaith Hamilton Pleasure Scale (SHAPS). The SHAPS will be collected at all study visits including week 12 follow-up. It will be used to screen subjects for having anhedonia as part of inclusion/exclusion assessment.

  2. Behavioral measure of anhedonia using the Probabilistic Reward Task [ Time Frame: 8 weeks ]
    To evaluate the impact of CERC-501 relative to placebo on a behavioral measure of anhedonia using the Probabilistic Reward Task (PRT). The PRT will be carried out at baseline and after 8 weeks of double-blind treatment to assess the effects on a behavioral outcome measure that assessed reward-related function.



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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 21 and 65 years of age
  • Must meet DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) diagnostic criteria for: Major Depressive Disorder, Bipolar I or II Depressed, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, or Post Traumatic Stress Disorder
  • Snaith-Hamilton Pleasure Scale (SHAPS) score ≥ 20
  • Reliable and willing to be available for the duration of the study
  • Willing and able to give written informed consent to participate
  • Able to understand and comply with instructions
  • If female of childbearing potential, must agree to use dual methods of contraception and be willing and able to continue contraception for 6 weeks after the last dose of study drug. Females using oral contraception must have started using it at least 2 months prior to the Baseline Visit
  • If male of childbearing potential, must have undergone surgical sterilization (such as a vasectomy) or agree to use a condom used with a spermicide during participation in the study and for 1 month afterward

Exclusion Criteria:

  • Expected to require hospitalization during the course of the study
  • Current/history of a psychotic disorder, current manic or mixed episode, autism spectrum disorders, mental retardation
  • Met DSMIV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria for substance abuse within the last 3 months or substance dependence within the last 6 months, excluding caffeine and/or nicotine
  • History of unstable or untreated serious medical condition based on physician evaluation, medical history, and screening laboratory testing
  • Active suicidal intent or plan, or history of attempt within the past 3 months based on physician evaluation and Columbia Suicide Severity Rating Scale (C-SSRS)
  • Use of any antidepressant, antipsychotic, anxiolytic, anticonvulsant, mood stabilizing, muscle relaxant, centrally acting antihistaminergic, stimulant or insomnia medications (See Appendix 2) within 5 half-lives of baseline or at any time during after baseline
  • Use of any medication that is primarily metabolized by Cytochrome P450 2C8 within 14 days of baseline or at any time during the study. This includes: Cerivastatin, Paclitaxel, Repaglinide, Sorafenib, Rosiglitazone, Trimethoprim, Amodiaquine, Morphine, Amiodarone, Cabazitaxel, Carbamazepine, Chloroquine, Ibuprofen, Trepostinil, Torsemide.
  • Any contraindications to the magnetic resonance imaging procedures
  • Positive urine drug screen at any time during the study
  • Use of any investigational medication within 3 months prior to the start of this study or scheduled to receive an investigational drug other than the study drug during the course of this study
  • Known hypersensitivity to CERC-501 (formerly known as LY2456302)
  • History of severe allergies or multiple adverse drug reactions
  • History of gastric disease (including peptic ulcer disease, gastritis, upper GI bleeding, or any GI precancerous condition), current clinically evident gastrointestinal complaints, or positive urea breath test
  • Current use of a proton pump inhibitor or histamine 2 blocker, or a history of chronic NSAID (nonsteroidal anti-inflammatory drug) use.
  • History of use of Salvia divinorum or use of Salvia divinorum at any time during the study.
  • Any other condition that in the opinion of the investigator would preclude participation in the study
  • Any smoking of cigarettes or use of other nicotine containing products within the last month or at any time during the study
  • Pregnant or lactating

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02218736


Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06510
United States, Indiana
Andrew Goddard, MD
Indianapolis, Indiana, United States, 46202-l7176
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
CaseWestern Reserve University
Cleveland, Ohio, United States, 44106
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 70030
Sponsors and Collaborators
Duke University
Yale University
Baylor College of Medicine
Indiana University
Icahn School of Medicine at Mount Sinai
Case Western Reserve University
Investigators
Principal Investigator: Richard D Weiner, MD, PhD Duke University

Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02218736     History of Changes
Other Study ID Numbers: Pro00052485
HHSN271201200006I ( Other Identifier: NIH/NIMH )
First Posted: August 18, 2014    Key Record Dates
Last Update Posted: March 26, 2018
Last Verified: March 2018

Keywords provided by Duke University:
Anhedonia
Mood and Anxiety Spectrum Disorders
CERC-501 (investigational product)
Kappa Opioid Receptor (KOR)

Additional relevant MeSH terms:
Disease
Anxiety Disorders
Phobic Disorders
Pathologic Processes
Mental Disorders
Analgesics, Opioid
Narcotic Antagonists
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents