The BIomarker Guided Study for Depression — BIG  

Major Depressive Disorder Clinical Trial

Official title: Precision Mental Health: Evaluating Biotype-guided Interventions for Depression

Status Recruiting

Clinical Trial Summary

The diagnosis of major depression relies on patient reports, and two patients with the same diagnosis might share only one symptom. Thus, a single mechanism is unlikely to underlie a broad descriptive diagnosis such as major depression. Our approach is anchored by a neural circuit taxonomy that proposes distinct biotypes of depression derived from functional magnetic resonance imaging (fMRI) (Williams et al., 2016). In this study, we aim to target a putative type of major depression that arises from dysfunction in cognitive control neural circuitry with a drug called guanfacine.

Clinical Trial Description

The flow of procedures and study visits is as follows:

1. Recruitment and screening: Participants experiencing depressive symptoms and not taking any psychiatric medications as determined by a 5 half life wash out period will be recruited from the community, including students and employees at Stanford. Recruitment will come primarily from Facebook ads, which will use only IRB approved material. The flyer will also be physically posted on boards in public locations in order to include a variety of sources for the study.

2. Individuals will need to participate in 2 to 3 screening visits (screening visit 2 and 3 can be combined) in order to enroll in the study. During the first visit, participants will go over informed consent, be administered a clinical interview and complete cognitive testing.

3. The second visit will be a medical screen in order to ensure participants are safe to continue and will include blood samples, medical history, vitals and a urine drug test and can be combined with visit three, detailed in step 4 below.

4. If the participant meets medical and cognitive criteria, scans for functional MRI will be undertaken at another study visit (or in combination with the medical screen) at the CNI on the Stanford campus. All MRI scans, including the optional MRI scan at week 6, will last 1.5 hours. If a participant's task-evoked activity in the DLPFC falls within the highest or lowest quartiles derived from a large data set of healthy volunteers, the participant will be able to proceed with medication

5. Participants will be randomized to either receive active medication treatment with guanfacine or placebo in a double blinded fashion. Randomization will be generated using a random number generator computer program. The probability for random assignment to each treatment is 50% chance randomized to active treatment with guanfacine and 50% chance randomized to placebo. A prescription lasting a period of 4 weeks will be sent to the Stanford Psychiatry Department from Mariner pharmacy. The pharmacist will provide a research coordinator in the lab with the randomization information, but this research coordinator will not be involved in patient interaction. The packaging of the medication itself will not identify drug or otherwise, but have an ID only.

6. At weeks 1, 3 and 5 when subject is not seen by the study MD, the participant will be monitored by an appropriately trained clinical research coordinator. All subjects will have an fMRI scan during week 4 and an optional week 6 fMRI scan. During in-person visits and phone monitoring, participants will be assessed for changes to physical health and treatment physical side-effects, anthropometrics and vital signs, changes to current medications (other than GIR), compliance to GIR treatment, alcohol and drug use abstinence compliance, birth control usage compliance and likelihood of pregnancy (female participants of child bearing potential), mood changes (QIDS-SR), suicidality (C-SSRS), clinical global impression severity (CGI-S) and improvement (CGI-I), Barratt Impulsiveness Scale (BIS). We will also have participants complete the following cognitive measures described below on a weekly basis during the treatment period in the form of an online battery (aka Webneuro): Choice reaction time, emotion test, digit span, GoNoGo, Verbal Interference, CPT, and Maze.

DETAILS

1. Participants: Volunteers will be aged 18-65 years old. The effect size of guanfacine vs. placebo on ADHD symptoms, including symptoms of inattention, has been estimated to be between 0.43 and 0.86. Using the most conservative of these values (0.43) and assuming an alpha of 0.05 with 4 groups, a total of 64 patients will be needed to provide a power of 80%. This would result in 32 subjects in each of the highest and lowest quartile groups of DLPFC activity.

2. Randomization: Participants will undergo fMRI scanning using tasks described below, including the N-back Working Memory Task. A region of interest (ROI) analysis will be performed using our established methods, to identify BOLD- dependent signal change in the DPLPC (right, left). Beta values for each ROI will be extracted for each subject and used to determine eligibility for the study. If a subject falls with the extreme quartiles of either the right or left DLPFC or both, this individual be randomized in a double blind fashion into one of two groups: placebo or guanfacine.

3. Suicidal thoughts or psychotic symptoms: Established procedures are in place for direct and immediate referral and intervention when suicidality and/or psychosis are identified.

4. Participants wishing to participate in this study will be screened with a psychiatric interview, an in-person physical exam (height, weight, vital signs, systems assessment, general appearance), medical history (history of disorders, diseases and allergies), lab tests (hematology: hemoglobin, hematocrit, total and differential WBC count, platelet count; chemistry: sodium, potassium, chloride, CO2, glucose, creatinine, BUN/urea; liver panel: albumin, total bilirubin, direct bilirubin, AST, ALT, ALP, total protein; endocrine: TSH; pregnancy test; full urine toxicology).

5. Participants will be prescribed tabs containing either placebo or guanfacine immediate release to be taken for 4 weeks and will be monitored by one of the study psychiatrists. Subjects randomized to GIR will start with 0.25mg GIR upon waking and increase by 0.25mg every other day with a goal dose of 2mg. If intolerance is encountered with a dosage increase, the dosage will be reduced to the prior level for a length to be determined by the treating psychiatrist and then raised again if/when tolerated. Dosing schedule may be slowed at the discretion of the physician based on participant's reaction to the drug. Decision to terminate guanfacine treatment will be made by clinicians based on side effects or lack of response or at patient's request. Follow up care for 2 weeks will be provided and transfer of care arranged at week 6 according to patients' decisions. At 4 weeks, the blind will be broken and those taking GIR may choose to continue this medication or taper off. If patients select to continue, a fMRI scan will be offered at week 6. Abrupt discontinuation of GIR (either due to side effects or to study end) will be avoided to prevent rebound hypertension and withdrawal symptoms. Participants will be seen by the study's psychiatrists at treatment weeks 2, 4, and 6. ;

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

• NCT number: NCT04181736
• Study type: Interventional
• Source: Stanford University
• Contact: Laura M Hack, MD, PhD
• Phone: 4102742582
• Email: lhack@stanford.edu
• Status: Recruiting
• Phase: Phase 4
• Start date: July 1, 2022
• Completion date: December 31, 2024