Dimensional Approach to Evaluate Reward Processing in Major Depressive Disorder Pre- and Post-Desvenlafaxine Treatment

NCT02859103 | Completed Phase 4

• 1 other identifier: DVS-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Anhedonia (the lack of pleasure in normally pleasurable things) is a common symptom of major depressive disorder (MDD), and it may impact how patients with depression experience reward. Understanding how anhedonia is related to the experience of reward may help improve how depression is treated. Computer tasks can be used to measure how reward is experienced, and these measures might be able to predict things like who is likely to become depressed, or who will respond to antidepressant medication. Studying the relationship between anhedonia and reward in patients with depression might also tell us something about how to improve diagnosis and treatment of other psychiatric disorders.This is an open label controlled treatment study lasting 8 weeks. The brain scans will be used to find changes in brain areas that may be related to how people perform on the tasks. The investigators goal is to use this information to help us find a reliable predictor that can be used to guide MDD treatment.

Conditions

Depression; Anhedonia

Outcome Measures

Primary Outcomes (6)

• Measuring Reward association and valuation using the Reward Association Task

  Based on signal detection theory, it evaluates response bias as a function of prior reward and permits an objective assessment of disorder-related sensitivity to reward. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways

  Change from Baseline at 8 Weeks

• Measuring Expectation using a prediction error task, to measure learning and choosing, during functional Magnetic Resonance Imaging (fMRI)

  This distinction was included in the design in order to dissociate potentially different neural circuits subserving learning reward associations and using them to guide behavior. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways

  Change from Baseline at 8 Weeks

• Anticipation of reward using the monetary incentive delay during fMRI

  This task was designed to disentangle anticipatory vs. consummatory phases of reward processing. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways

  Change from Baseline at 8 Weeks

• Motivation/effort using the Cued-Reinforcement Reaction Time Task and the EEfRT task.

  The Cued-Reinforcement Reaction Time Task (CRRT) provides an evaluation of reward-based reaction time speed as an index of incentive motivation.The EEfRT task allows analysis of the predictive value of reward probability and magnitude on effort-based decision making. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways

  Change from Baseline at 8 Weeks

• Pleasure/Liking using the monetary incentive delay task in an fMRI

  This task was designed to disentangle anticipatory vs. consummatory phases of reward processing. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways

  Change from Baseline at 8 Weeks

• Feedback integration using the Probabilistic Reversal Learning task during fMRI

  participants are presented with a choice of two stimuli. Based on their first choice, the selected stimulus will be rewarded with a high probability, while the other will be rewarded with a low probability.To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways

  Change from Baseline at 8 Weeks

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Patients in this arm will receive treatment with desvenlafaxine for 8 weeks.

Drug: Desvenlafaxine

Healthy Control

NO INTERVENTION

Patients in this arm are healthy controls and will not receive any medication.

Interventions

Desvenlafaxine DRUG

Patients will be provided 50mg dose of desvenlafaxine for 1 week titrated up to 100mg dose of desvenlafaxine for 7 weeks.

Also known as: Pristiq

Treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• DSM-5 criteria for Major Depressive Episode (MDE) within a MDD, confirmed through MINI diagnosis
• Age between 18 and 60 years
• Hamilton Depression Rating Scale - 17 item (HRSD-17)58 \> 17 (moderate to severe symptoms)
• Free of psychotropic medications for at least 5 half-lives before baseline visit
• Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)
• Pregnancy/lactation
• Medical condition requiring immediate investigation or treatment
• Recent (\< 6 months)/current history of drug abuse/dependence (other than caffeine, or nicotine)
• Lifetime history of psychosis, other Axis I comorbidities are allowable
• Significant Axis II diagnosis
• Previous intolerance or failure to respond to an adequate trial of desvenlafaxine
• Failure of \> 2 antidepressant treatments of adequate dose and duration for current MDE
• Age between 18 and 60 years
• Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)
• Pregnancy/lactation

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1M8, Canada

Location

MeSH Terms

Conditions

Depression; Anhedonia

Interventions

Desvenlafaxine Succinate

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Lipids

Study Officials

• Sakina Rizvi, PhD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist

Study Record Dates

• First Submitted: July 15, 2016
• First Posted: August 8, 2016
• Study Start: June 1, 2017
• Primary Completion: November 4, 2019
• Study Completion: November 4, 2019
• Last Updated: November 2, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)