Clinical Trial: Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 th

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.

Detailed Summary:

FAST-MAS addresses an important problem and critical barrier to progress in Mood and Anxiety Spectrum Disorders and if the aims of the project are achieved, FAST-MAS could shift scientific knowledge, technical capacity, and clinical practice in a positive direction.

The Mood and Anxiety Spectrum disorders are both extremely common and associated with significant morbidity and mortality and, as such, represent an important public health problem in the United States.

The mood disorders include the following diagnostic entities: major depressive disorder (MDD), bipolar disorder (including subtypes of mania, mixed state, and depressed, as well as types I and II), and dysthymic disorder. Available epidemiologic data suggest that the prevalence of these mood disorders is extremely high among adults in the United States, approaching 10%. Among the mood disorders, MDD has high lifetime prevalence, with recent estimates up to 16%. According to the World Health Organization (WHO), MDD is currently the leading cause of disability with the greatest burden of illness in developed countries and the third most common cause of disability worldwide. MDD is life shortening due to both suicide and its association with increased mortality from other medical conditions. It is also a highly recurrent condition with between 50% and 75% of persons diagnosed with MDD experiencing more than one episode. Bipolar Disorder is also a highly recurrent condition. The lifetime prevalence of bipolar disorder has been estimated to be approximately 3.4% in the World Health Survey Initiative. Approximately 60% of affected individuals experience severe or very severe role impairment based on the Sheehan Disability Scale and, like MDD, bipolar disorder is associated with significant suicide risk.

The anxiety dis
Sponsor: Andrew Krystal

Current Primary Outcome: 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.


Original Primary Outcome:

  • Reward-Related Circuit Engagement POC Outcome for the study will be task-related fMRI (functional magnetic resonance imaging) ventral striatal (e.g., nucleus accumbens) activation occurring with reward and anticipation during the Monetary Incentive Delay [ Time Frame: Baseline ]
    Baseline reading prior to drug dosing
  • Reward-Related Circuit Engagement POC Outcome for the study will be task-related fMRI ventral striatal (e.g., nucleus accumbens) activation occurring with reward and anticipation during the Monetary Incentive Delay (MID) Task [ Time Frame: Week 8 ]
    Reading on last day of drug dosing


Current Secondary Outcome:

  • 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.
  • 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.


Original Secondary Outcome:

  • Clinical Anhedonia Outcome for this study will be the total score Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Screening ]
    To assess anhedonia
  • Clinical Anhedonia Outcome for this study will be the total score Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Baseline ]
    To assess anhedonia
  • Clinical Anhedonia Outcome for this study will be the total score Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Week 2 ]
    To assess anhedonia after 2 weeks of drug or placebo
  • Clinical Anhedonia Outcome for this study will be the total score Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Week 4 ]
    To assess anhedonia after 4 weeks of study drug or placebo
  • Clinical Anhedonia Outcome for this study will be the total score Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Week 6 ]
    To assess anhedonia after 6 weeks of study drug or placebo
  • Clinical Anhedonia Outcome for this study will be the total score Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Week 8 ]
    To assess anhedonia after 8 weeks of study drug or placebo
  • Clinical Anhedonia Outcome for this study will be the total score Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Week 12 ]
    To assess anhedonia after study drug or placebo has been stopped for 4 weeks
  • Behavioral Anhedonia Outcome for this study will be Response Bias and Reward Learning Scores on the Probabilistic Reward Task (PRT) [ Time Frame: Baseline ]
    Used to assess participant's propensity to modulate behavior of a function of reinforcement history
  • Behavioral Anhedonia Outcome for this study will be Response Bias and Reward Learning Scores on the Probabilistic Reward Task (PRT) [ Time Frame: Week 8 ]
    Used to assess participant's propensity to modulate behavior as a function of reinforcement history after 8 weeks of therapy with study drug or placebo. Will be compared to results obtained at baseline.


Information By: Duke University

Dates:
Date Received: August 15, 2014
Date Started: June 2015
Date Completion: September 2017
Last Updated: November 23, 2016
Last Verified: November 2016