Pharmacological Modulation of Hippocampal Activity in Psychosis 2

Schizophrenia; Psychosis Clinical Trial

Official title:

Pharmacological Modulation of Hippocampal Activity in Psychosis 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04559529
• Other study ID #: VEPP_200915
• Status: Completed
• Phase: Phase 2
• Start date: September 23, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test whether administration of levetiracetam (LEV), a commonly used anti-epileptic that alters neurotransmitter release, can reduce hippocampal hyperactivity in people with psychotic disorders. Specifically, the investigators will utilize two functional magnetic resonance imaging (MRI) techniques: 1) blood-oxygen-level-dependent (BOLD) contrast will assess activity with a visual scene processing task that engages the anterior hippocampus and 2) arterial spin labeling (ASL) will assess baseline activity. Previous studies in people with psychotic disorders have shown that the hippocampus is hyperactive and more activity correlates with worsening of clinical symptoms. Therefore, the aim of this study is to use an intervention to further understand the underlying mechanisms of the hippocampus in psychosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Inclusion criteria for psychosis subjects

1. Men and women age 18 - 65.

2. Communicative in English.

3. Provide voluntary, written informed consent.

4. Physically healthy by medical history.

5. BMI > 17.5 and < 45.

6. Diagnosis of a psychotic disorder confirmed by Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID) or diagnostic interview with a trained clinician.

7. Stable medication regimen over at least the past two weeks, including the use of either an oral or intramuscular administration of an antipsychotic medication.

8. For females, no longer of child-bearing potential, or agreeing to practice effective contraception during the study (e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository; male partner sterilization; or true abstinence when this is in line with the preferred and usual lifestyle of the subject); and,

9. For females of child-bearing potential, must have a negative urine pregnancy test before MRI and drug administration.

10. Not breastfeeding/nursing at time of screening or at any time during the study.

Inclusion criteria for healthy controls

1. All of the above except for subjects will be psychiatrically healthy and not taking psychotropic or potentially psychoactive prescription medication.

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Exclusion Criteria:

Exclusion criteria for psychosis subjects

1. Age less than 18 or greater than 65.

2. Not communicative in English.

3. Unable to provide written informed consent.

4. Current medical or neurological illness.

5. History of severe head trauma.

6. BMI < 17.5 or > 45.

7. Meets criteria for diagnosis of substance or alcohol use disorder within the past month.

8. Positive urine pregnancy test during the study.

9. Breastfeeding/nursing at time of screening or at any time during the study.

10. Conditions that preclude MR scanning (as defined in the Screening Form)

11. Conditions that preclude study drug administration (as defined in the Screening Form)

Exclusion criteria for healthy controls

All of the above and in addition:

1. Current use of psychotropic or potentially psychoactive prescription medication.

2. Major psychiatric disorder as determined by Diagnostic and Statistical Manual -5 (major depression, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, etc)

Related Conditions & MeSH terms

• Mental Disorders
• Psychotic Disorders
• Schizophrenia
• Schizophrenia; Psychosis

Intervention

Drug:
• Levetiracetam (LEV) 500 mg
The levetiracetam pill will look just like the placebo pill.
• Placebo
The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Levetiracetam (LEV)	ASL signal after LEV, using Magnetic Resonance Imaging (MRI) scanning of the brain. ASL measures cerebral blood flow, which is linked to neuronal metabolism and functions as a proxy for neuronal activity.	2 hours after LEV administration
Primary	Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Placebo	ASL signal after placebo, using Magnetic Resonance Imaging (MRI) scanning of the brain. ASL measures cerebral blood flow, which is linked to neuronal metabolism and functions as a proxy for neuronal activity.	2 hours after placebo administration
Primary	Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Levetiracetam (LEV)	BOLD signal after LEV, using Magnetic Resonance Imaging (MRI) scanning of the brain. This method reflects changes in oxygenation of blood in the brain during a scene-processing task that engages, or recruits, the hippocampus.	2 hours after LEV administration
Primary	Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Placebo	BOLD signal after placebo, using Magnetic Resonance Imaging (MRI) scanning of the brain. This method reflects changes in oxygenation of blood in the brain during a scene-processing task that engages, or recruits, the hippocampus.	2 hours after placebo administration