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Anhedonia, Development, and Emotions: Phenotyping and Therapeutics (ADEPT)

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ClinicalTrials.gov Identifier: NCT05487885
Recruitment Status : Recruiting
First Posted : August 4, 2022
Last Update Posted : August 4, 2022
Sponsor:
Information provided by (Responsible Party):
Erika Forbes, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE July 27, 2022
First Posted Date  ICMJE August 4, 2022
Last Update Posted Date August 4, 2022
Actual Study Start Date  ICMJE July 22, 2022
Estimated Primary Completion Date November 15, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2022)
  • Montgomery-Asberg Depression Rating Scale (MADRS) change in score [ Time Frame: change from Baseline to 12 months post-TMS ]
    Assess depression severity, the higher the score, the more significant the depression is score ranges 0-60 MADRS score must be greater than or equal to 12
  • Montgomery-Asberg Depression Rating Scale (MADRS) change in score [ Time Frame: change from Baseline to 12 months post-ketamine ]
    Assess depression severity, the higher the score, the more significant the depression is score ranges 0-60 MADRS score must be greater than or equal to 12
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2022)
  • Snaith Hamilton Pleasure Scale (SHAPS) score [ Time Frame: change from Baseline to 12 months post-TMS ]
    Assess anhedonia, the higher the score, the higher anhedonia (highest is 14) score ranges 0-14
  • Snaith Hamilton Pleasure Scale (SHAPS) score [ Time Frame: change from Baseline to 12 months post-ketamine ]
    Assess anhedonia, the higher the score, the higher anhedonia (highest is 14) score ranges 0-14
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anhedonia, Development, and Emotions: Phenotyping and Therapeutics
Official Title  ICMJE Anhedonia, Development, and Emotions: Phenotyping and Therapeutics (ADEPT) Study
Brief Summary

The goal of the ADEPT Study is to understand anhedonia in young people and how it changes based on treatments targeting the brain circuit underlying it. Anhedonia is a challenging mental health symptom that involves difficulty with motivation to experience pleasant events. This study could help develop treatments for people whose depression does not improve with traditional treatments.

The ADEPT Study includes two phases. In Phase 1, participants are asked to go through a series of activities to measure anhedonia, including MRI scans, blood draws, behavioral tasks, clinical interviews, questionnaires, and app-based assessments of experiences and behaviors. Phase 2 involves therapeutic activities, such as transcranial magnetic stimulation (TMS), positive affect training, and, for some people, ketamine administration. If the participant qualifies and is interested, they may choose to do Phase 2 activities in addition to Phase 1.

Detailed Description

In this research study, the investigators are trying to understand and change anhedonia in young people with depression. Anhedonia is experienced by many people who have depression, and it involves difficulty with motivation, energy, and anticipation of pleasant events. People who experience anhedonia often have more severe depression, experience depression for longer periods of time, and don't easily get better with traditional treatments. The investigators want to understand anhedonia early in life in order to help young people develop along healthy pathways and avoid chronic illness. Anhedonia is related to function in the brain's reward circuit, inflammation in the body, and people's experiences and behaviors, and will measure all of these. The investigators also want to understand anhedonia by using treatments that could improve it. To do that, activities will be used that have been used to treat depression and target the brain's reward circuit, which is believed to be the source of anhedonia. Finally, anhedonia will be measured over approximately 1 year to see how it changes with time, development, or treatment-based experiences. Eventually, the findings of this study might be useful for treating depression and improving people's quality of life.

The study is looking for 300 young people (aged 15-25) who are currently experiencing depression to participate in our research study. In Phase 1 of our study, a series of activities will be conducted to understand the characteristics of anhedonia, including MRI scans, blood draws, behavioral tasks, clinical interviews, questionnaires, and measurement of real-life experiences and behavior using a phone app. This is called "phenotyping" because these characteristics are also called phenotypes.

The eligibility process for Phase 1 will include an interview with questions about the participant's mood, experiences, and behaviors. This interview will take approximately 2-3 hours. With permission, interviews will be video recorded to facilitate training and supervision of study staff. Participants will also be asked questions about health, including treatment history.

Study procedures include 4 visits over approximately 1 year. These may be broken into two sessions per visit for scheduling reasons. In addition, the study will include an ongoing smartphone app-based assessment of mood, experiences, and behavior.

Visit 1 consists of an MRI scan, questionnaires about thoughts, emotions, and experiences, tasks on a computer and a blood draw by a trained phlebotomist. Visits 2-4 consists of a second MRI scan, questionnaires, tasks on a computer, a blood draw by a trained phlebotomist, and an interview about mood, experiences, and behaviors.

Phase 2 of this study involves procedures that are therapeutic, meaning they can treat depression and anhedonia. These include transcranial magnetic stimulation (TMS), which is a noninvasive procedure to treat depression that uses magnetic fields to stimulate nerve cells in the brain. Visits with TMS will include Positive Affect Training, which involves changing behaviors and thoughts to build positive emotions. People whose depression does not improve with TMS may receive a single intravenous (IV, or into the vein) infusion of ketamine, a medicine that is used in hospitals for anesthesia and that can improve depression quickly.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

The study has a longitudinal design in which participants complete 2 sets of activities:

Phase 1: Phenotyping. This includes assessment with diagnostic interview, questionnaires, behavioral tasks, MRI, app-based digital assessment, and blood draw for inflammatory markers. This set of activities will occur at 4 time points over the course of 1 year/participant (study entry, approximately 4 months, approximately 5 months, and approximately 1 year), and all participants will complete them.

Phase 2: Therapeutic activities: (1) 10 theta burst stimulation (TBS) sessions (TBS 2 times/session) plus positive affect (PA) training for all participants; and (2) IV ketamine infusion for those who do not respond to TBS/PA activities.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Depression
  • Anhedonia
Intervention  ICMJE
  • Device: Continuous theta burst stimulation (cTBS)
    a form of transcranial magnetic stimulation, to dorsomedial prefrontal cortex (dmPFC)
  • Behavioral: Positive Affect Training
    Psychosocial add-on intervention that could enhance the effects of TBS. PA Therapy (Craske et al., 2016) is an innovative cognitive and experiential technique developed to address anhedonia specifically and, ideally, change altered patterns of frontostriatal function. Standing in contrast to Cognitive Behavioral Therapy, PA training has efficacy for enhancing positive affect and reducing negative affect (Craske et al., 2018). This treatment can be easily applied, and we propose that it will enhance neural circuit-level changes elicited by TBS.
  • Drug: Ketamine Injectable Solution
    Ketamine is FDA-approved as an anesthetic agent that will be used off-label in this study. It is used routinely in both pediatric and adult patients and is considered extremely safe in substantially higher, anesthetic doses. The dose to be administered here (0.5 mg/kg) is a much lower, subanesthetic dose, and the administration route (intravenous) is the standard when used in anesthesia. Published studies and metaanalyses of this dose of intravenous ketamine as an off label use in depression show clearly that there are no increased risks in this population, including a recent study in adolescents (Dwyer et al, 2021, American Journal of Psychiatry). A single dose of ketamine will be used to determine if it alters the functioning of the anhedonia-related reward functioning and frontostriatal biomarkers assessed in this study.
Study Arms  ICMJE
  • Experimental: TMS and PAT
    All open label with no randomization to placebo
    Interventions:
    • Device: Continuous theta burst stimulation (cTBS)
    • Behavioral: Positive Affect Training
  • Experimental: TMS and PAT, then Ketamine
    All open label with no randomization to placebo
    Interventions:
    • Device: Continuous theta burst stimulation (cTBS)
    • Behavioral: Positive Affect Training
    • Drug: Ketamine Injectable Solution
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 3, 2022)
275
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2025
Estimated Primary Completion Date November 15, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Phase 1 (all participants)

  • Current DSM-5 depressive disorder
  • Severity ≥ 12 on MADRS
  • Moderate-severe anhedonia (75% of sample) or low anhedonia (25% of sample)

Phase 2 (for participants in TBS and ketamine phase, in addition to above)

• ≥ 1 failed antidepressant trial (for qualification for Phase 2 of study and definition of non-response to TMS in order to be eligible for ketamine) = Treatment for at least 6 weeks with an antidepressant medication reaching recommended dosage for adults for at least 3 weeks of the treatment (e.g., 20 mg fluoxetine)

Exclusion Criteria:

Phase 1 (all participants)

  • Lifetime psychosis, bipolar disorder, autism spectrum disorder, or developmental disorder
  • Serious, unstable neurological disorder (e.g., seizure disorder)
  • Brain injury with loss of consciousness
  • Daily nicotine use
  • Moderate-severe substance use disorder, past 6 mos.
  • MRI contraindications (e.g., metal in body)

Phase 2 (for participants in TBS and ketamine phase, in addition to above)

  • Serious, unstable respiratory or cardiovascular illness
  • Pre-TBS: Alcohol binge in past week or > 3 drinks/day in past 3 days
  • Pre-ketamine: use of MAOIs in past 2 weeks
  • Medication: SNRIs, bupropion, antipsychotics, or stimulants
  • Pregnancy
  • High blood pressure
  • Current illicit stimulant use
  • Lifetime recreational ketamine or PCP use
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ashley Pogue, BA 248-912-7458 pogueam@upmc.edu
Contact: David Rogers rogersd4@upmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05487885
Other Study ID Numbers  ICMJE STUDY21120080
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Erika Forbes, University of Pittsburgh
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Erika Forbes
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Erika E Forbes, PhD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP