Performance and FMRI BOLD Signal Changes in Impulsive Patients

A Trial to Explore Performance and FMRI BOLD Signal Changes During Impulsivity Tasks in Impulsive Patients with Attention Deficit Hyperactivity Disorder and Borderline Personality Disorder

This study is a preceding study conducted to validate the methodology for assessing impulsivity by tasks and task-based fMRI measurements in patients with Attention Deficit Hyperactivity Disorder (ADHD) or Borderline Personality Disorder (BPD).

It is planned to conduct a clinical trial to test pharmacodynamic effects of a new drug under development for impulsivity including patients with ADHD or BPD. For the preparation of this planned trial, a preceding study will be conducted. The results of this preceding study will be needed to prepare and plan the upcoming proof-of-clinical-principle-study regarding behavioral effects, involved brain regions, effect sizes, patient experience, and task design. Testing and optimizing the study procedures in advance in this preceding study will help to define the objectives and endpoints of the planned pharmacodynamic trial.

Inclusion Criteria:

1. meet current DSM-5 criteria for ADHD or BPD as a primary diagnosis as assessed by SCID and SCID-PD
2. between 18 and 45 years, inclusive
3. BIS-11 score of ≥ 70
4. completely fluent German speaker who, in the opinion of the Investigator, is capable of completing the fMRI and behavioral tasks
5. must have signed the informed consent form prior to the first study-related procedure indicating they understand the purpose of, and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

1. Lifetime diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar I or II disorder, delusional disorder, or autism spectrum disorder as confirmed by the SCID at screening visit

2. Moderate or severe substance use disorder within the last 6 months.

3. Any other psychiatric disorder that is not currently stable in symptoms and treatment. Stable is defined as have no significant changes in symptom acuity or medication treatment in the 3 months prior to enrollment

4. Positive results on a urine drug screen or alcohol breath test, or any signs or symptoms of acute intoxication at screening or enrollment visit

5. A female subject with a positive pregnancy test at screening or enrollment visit

6. Unstable medical condition, history of seizure disorders, stroke, brain tumor, or any other major neurological illness

7. Subjects deemed to be at significant risk of serious violence or suicide based on any one of the following:

   • Significant risk of committing violent acts, homicide, serious self-harm, or suicide based on history, routine psychiatric status examination, or according to the investigator's experience OR
   • Any suicide attempt in the past 6 months (i.e. actual attempt, interrupted attempt, aborted attempt) prior to enrollment OR
   • Any suicidal ideation of type 4 or 5 in the Columbia-Suicide Severity Rating Scale (C-SSRS) in the past 6 months prior to enrollment

8. Subjects not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (that, in the investigator's opinion, makes the subject an unreliable trial subject)

9. Concomitant use of restricted psychotropic medication. All restricted psychotropic medications must be washed out at least 5 half-lives prior to enrollment (including ADHD medications such as amphetamine or methylphenidate derivates). Allowed medications must be stable in agent, dose, and frequency for > 3 month prior to enrollment:

   • a single antidepressant of the Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin-Noradrenaline Reuptake Inhibitor (SNRI) class
   • A single second-generation antipsychotic at a low dose (1 thorazine dose equivalent or less, which translates to ≤ 2 mg/day for risperidone, 5 mg/day for olanzapine, 75 mg/day for quetiapine, 60 mg/day for ziprasidone, and 7.5 mg/day for aripiprazole)
   • Permitted sleep medications must be nightly scheduled medications (not PRN) and may include non-benzodiazepines, antihistamines, melatonin, trazodone, low dose doxepin (≤ 50mg), and low dose quetiapine (≤75mg qhs).

10. Any contraindication to undergo an MRI radiography (e.g. history of surgery involving metal implants), including but not limited the following:

    • A planned medical treatment within the study period that might interfere with the study procedures
    • Subjects who have undergone operations to the head
    • Subjects with significant hearing impairments which, in the opinion of the investigator, may interfere with the performance of fMRI tasks
    • Subjects with a significant visual impairment including color blindness, or history of ocular treatment including corrective laser eye surgery, or ongoing condition, which in the opinion of the investigator may interfere with the performance of the behavioral or fMRI tasks

11. Subject is a staff member or the relative of a staff member or is in a subordinate relationship with the Investigator

12. Signs or symptoms of Post-Covid disease

13. Inability or unwillingness to comply with study procedures, including study prohibitions and restrictions

14. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

15. Vulnerable subject who lives in an institution on court or authority order

16. Participation in another clinical trial.