Clinical trial NCT05487885: Anhedonia, Development, and Emotions: Phenotyping and Therapeutics
Official title: Anhedonia, Development, and Emotions: Phenotyping and Therapeutics (ADEPT) Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Depression
Anhedonia
Keywords: depression
anhedonia
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2022-08-04
Enrollment: 123
Sex: ALL
Minimum age (years): 15
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS) score
timeFrame: pre- to post-TMS (over 2 weeks)
Secondary outcomes:
measure: Snaith Hamilton Pleasure Scale (SHAPS) score
timeFrame: pre- to post-TMS (over 2 weeks)
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Loeffler Building
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Erika E Forbes, PhD
role: PRINCIPAL_INVESTIGATOR
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