Validating Reward-related Biomarkers (RTOC)

Depression Clinical Trial

— RTOC  

Official title:

Validating Reward-related Biomarkers to Facilitate Development of New Treatments for Anhedonia and Reward Processing Deficits in Schizophrenia and Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04024371
• Other study ID #: RTOC1
• Status: Completed
• Start date: September 16, 2019
• Est. completion date: February 1, 2021

Study information

• Verified date: July 2022
• Source: Maastricht University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Deficits or abnormalities in reward processing are present in a number of psychiatric disorders. The overarching objective of the study is to conduct initial validation work towards optimising three experimental tasks - which have previously been shown to be sensitive to reward processing deficits - for future use in clinical trials. This initial validation work has the primary objective to uncover group differences in task outcome measures between healthy control participants, participants with Major Depressive Disorder (MDD) and participants with schizophrenia (SZ) using statistical analyses. This may provide some indications for the use of these tasks as clinically-relevant biomarkers. Primary aims include: (i) comparing the investigator's endpoint means and distributions to those in previously published data; (ii) replication of previously-reported differences between MDD/SZ vs. healthy control participants, and, (iii) exploring the relationship between task endpoints and subjective participant- and clinician-rated report of reward-related constructs (e.g. anhedonia, negative symptoms).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 55 Years

Eligibility

General:

1. Be able to provide signed and dated informed consent for study participation.

2. Be male or female, aged between 20 and 55 years, inclusive.

3. Be able to read, write, and speak the language in which psychometric tests are provided, with acceptable visual and auditory acuity (corrected if necessary).

4. Unless otherwise stated, CNS medications to treat symptoms of MDD or SZ and other stable CNS conditions requiring medication is permitted in the MDD and SZ groups, provided the daily dose of medication has not been changed by more than +/- 30% in the last 4 weeks before the start of the study, and is not expected to change by a larger fraction while participating in the study. MDD

Participants must:

1. Have a primary Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnosis of MDD, confirmed by the result of the MINI interview conducted by the site at screening. Subjects with a diagnosis of comorbid Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), Panic Disorder or specific phobia may be included.

2. Meet the DSM-5 criteria for a current Major Depressive Episode, with the current depressive episode not having lasted longer than 6 months.

3. If undergoing treatment, be currently treated with an antidepressant approved in this protocol for at least 4 continuous weeks. Psychological treatments (e.g., Cognitive Behaviour Therapy, Interpersonal Psychotherapy, Psychodynamic Psychotherapy etc.) are all permitted in this study regardless of frequency and duration. SZ

Subjects must:

1. Have a primary diagnosis of schizophrenia according to the Statistical Manual of Mental Disorders 5th edition (DSM-5), confirmed by the result of the MINI interview conducted by the site at screening. Subjects with a diagnosis of comorbid Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), Panic Disorder or specific phobia may be included.

2. Dose of antipsychotics not exceeding the equivalent of 6 mg risperidone.

Related Conditions & MeSH terms

• Anhedonia
• Anhedonia, Physical
• Anhedonia, Social
• Depression
• Mental Disorders
• Motivation
• Negative Symptoms With Primary Psychotic Disorder
• Psychotic Disorders
• Schizophrenia

Intervention

Behavioral:
• Self-rating Questionnaires
Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al. 1995) Quick Inventory of Depressive Symptomatology (QIDS; 16 items) Behavioral avoidance/inhibition Scales (BIS/BAS)
• Measures of Reward processing/reinforcement learning
Grip Strength Effort Task (Reddy et al. 2015; in combination with EEG) Doors (Gambling) task (Foti and Hajcak 2009; in combination with EEG) Reinforcement Learning/Working Memory task (Collins et al. 2017; no EEG)
• Additional Schizophrenia-specific Questionnaires and Interviews
Positive and Negative Syndrome Scale (PANSS: Kay et al. 1987) Brief Negative Symptom Scale (BNSS; Kirkpatrick et al. 2011)

Locations

Country	Name	City	State
Germany	University Hospital Frankfurt, Department of Psychiatry, Psychosomatic Medicine and Psychotherap	Frankfurt
Greece	Aristotle University of Thessaloniki, School of Medicine, Department of Clinical Pharmacology	Thessaloníki
Netherlands	Maastricht University	Maastricht
Spain	Institute of Neuropsychiatry and Addictions (INAD), Parc de Salut Mar, Barcelona	Barcelona

Sponsors (7)

Lead Sponsor	Collaborator
Maastricht University	Aristotle University Of Thessaloniki, Biotrial, Maastricht University, School for Mental Health and Neuroscience, P1vital Products LTD., The Institute of Neuropsychiatry and Addictions (INAD), Parc de Salut Mar, Barcelona, University Hospital Frankfurt, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy

Countries where clinical trial is conducted

Germany,  Greece,  Netherlands,  Spain, 

References & Publications (3)

Collins AGE, Albrecht MA, Waltz JA, Gold JM, Frank MJ. Interactions Among Working Memory, Reinforcement Learning, and Effort in Value-Based Choice: A New Paradigm and Selective Deficits in Schizophrenia. Biol Psychiatry. 2017 Sep 15;82(6):431-439. doi: 10.1016/j.biopsych.2017.05.017. Epub 2017 May 31. — View Citation

Foti D, Hajcak G. Depression and reduced sensitivity to non-rewards versus rewards: Evidence from event-related potentials. Biol Psychol. 2009 Apr;81(1):1-8. doi: 10.1016/j.biopsycho.2008.12.004. Epub 2008 Dec 31. — View Citation

Reddy LF, Horan WP, Barch DM, Buchanan RW, Dunayevich E, Gold JM, Lyons N, Marder SR, Treadway MT, Wynn JK, Young JW, Green MF. Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1-Psychometric Characteristics of 5 Paradigms — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grip effort outcome	Percentage of hard task choices at different reward levels	Day 1
Primary	Doors task outcome	"Feedback negativity", an event-related potential (ERP) at approximately 300ms after feedback presentation indicating a favourable versus unfavourable outcome in paradigms in which the participant loses or wins money.	Day 1
Primary	RL/WM task outcome	Accuracy as function of set size (difficulty)	Day 1