Exceptional Experiences (EE), Salience & Dopaminergic Neurotransmission

Sponsor

University of Zurich (Other)

Overall Status

Completed

CT.gov ID

NCT03333369

Collaborator

Swiss Federal Institute of Technology (Other)

Enrollment

Location

Arms

14.9

Actual Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The dopamine hypothesis of schizophrenia implies that alterations in the dopamine system cause functional abnormalities in the brain that may converge to aberrant salience attribution and eventually lead to psychosis. Indeed, widespread brain disconnectivity across the psychotic spectrum has been revealed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the dopaminergic involvement in intrinsic functional connectivity (iFC) and its putative relationship to the development of psychotic spectrum disorders remains partly unclear - in particular at the low-end of the psychosis continuum. Therefore, the investigators examined dopamine-induced changes in striatal iFC and their modulation by psychometrically assessed schizotypy. The randomized, double-blind placebo-controlled study design included 54 healthy, right-handed male participants. Each participant was assessed with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 min of rs-fMRI scanning. Participants then received either a placebo or 200 mg of L-DOPA, a dopamine precursor. The investigators analyzed iFC of six striatal seeds that are known to evoke modulation of dopamine-related networks.

The investigators hypothesized that, within the L-DOPA treatment group, the striatal iFC would be disrupted due to increased availability of dopamine. The investigators further hypothesized that individuals with high schizotypal scores would show a disruption of striatal connectivity, as has been reported with schizophrenia. In addition, the investigators hypothesized that the L-DOPA-dependent change in striatal iFC would interact with the severity of positive symptoms, as has been found in previous studies in non-clinical psychosis. The investigators anticipated this symptom-dependent change, especially in the ventral striatal regions, because these are thought to modulate cortico-striatal loops associated with cognition and emotion.

Condition or Disease	Intervention/Treatment	Phase
Healthy Schizotypal Personality	Drug: 200 mg levodopa/50 mg benserazide Drug: Dextrose	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

65 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Each subject in the group will participate in two test sessions, separated by at least one week. All sessions will start at 15:30. In a double-blind within-design procedure, participants will be randomly assigned to receive either a cachet of a dual-release formulation of 200 mg levodopa/50 mg benserazide (a peripheral L-dihhydroxyphenylalanine-decarboxylase inhibitor) or a placebo in the first session. In the second session they will receive the other intervention.Each subject in the group will participate in two test sessions, separated by at least one week. All sessions will start at 15:30. In a double-blind within-design procedure, participants will be randomly assigned to receive either a cachet of a dual-release formulation of 200 mg levodopa/50 mg benserazide (a peripheral L-dihhydroxyphenylalanine-decarboxylase inhibitor) or a placebo in the first session. In the second session they will receive the other intervention.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

For the randomization of the intervention and placebo the "Research Randomizer" on www.randomizer.org will be used. The randomization will be performed by the Kantonsapotheke in Zurich. The generated list of condition sequences will be stored at there. The list will not be accessible for study members who are associated with the assessment. The Boxes containing the cachets will be labelled with the subject number and A or B for the first or second session, respectively as well as with the ID of the study. The cachets will be prepared and labelled at the Kantonsapotheke in Zurich. DA and placebo will be provided in identical cachets. The blinding will be broken only after a subject has completed both experimental sessions or in case of an acute reaction during the session.

Primary Purpose:

Basic Science

Official Title:

L-Dopa Modulated Striatal Functional Connectivity in Schizotypal Adults: a Randomized Double-blind Placebo-controlled Study

Actual Study Start Date :

May 15, 2014

Actual Primary Completion Date :

Aug 13, 2015

Actual Study Completion Date :

Aug 13, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Madopar Arm A single dose of a cachet filled with 200 mg levodopa/50 mg benserazide	Drug: 200 mg levodopa/50 mg benserazide Other Names: Madopar DR
Placebo Comparator: Placebo Arm A single dose of a cachet filled with Dextrose	Drug: Dextrose Other Names: Placebo

Arm

Intervention/Treatment

Active Comparator: Madopar Arm

A single dose of a cachet filled with 200 mg levodopa/50 mg benserazide

Drug: 200 mg levodopa/50 mg benserazide

Other Names:

Madopar DR

Placebo Comparator: Placebo Arm

A single dose of a cachet filled with Dextrose

Drug: Dextrose

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

intrinsic functional connectivity [2 hours]
Dopamine dependent intrinsic functional connectivity as measured by resting-state functional magnetic resonance imaging

Secondary Outcome Measures

Schizotypy [15 min]
Schizotypy scores assessed by the Schizotypal Personality Questionnaire (SPQ): n of items 74 (min. score = 0 ; max. score = 74): higher score implies higher level of schizotypy Subscales: Cognitive Perceptual (min. score = 0 ; max. score = 33) Interpersonal (min. score = 0 ; max. score = 25) Disorganized (min. score = 0 ; max. score = 16)

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 60 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy,
Between 20 and 40 years of age,
With exceptional experiences or skeptics,
Caucasian origin,
Normal visual and acoustic accuracy.

Exclusion Criteria:

Persons with a personal or first-degree family history of neurological and psychiatric disease, including impaired cognitive abilities,
Pregnant or breastfeeding women,
Chronic or acute pain,
Acute or chronic somatic disease,
Women (i.e. only men included),
Men over 40 years of age or below 20,
left- or mixed-handedness,
General MRI exclusion criteria,
General Dopamine-Challenge exclusion criteria,
Hormonal or herbal therapy,
Smoker.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Collegium Helveticum, ETH & Universität Zürich	Zürich		Switzerland	8006 Zürich

Sponsors and Collaborators

University of Zurich
Swiss Federal Institute of Technology

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Zurich

ClinicalTrials.gov Identifier:

NCT03333369

Other Study ID Numbers:

DA_EE_Salience

First Posted:

Nov 6, 2017

Last Update Posted:

Nov 6, 2017

Last Verified:

Nov 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by University of Zurich

resting-state functional MRI

Dopamine

functional connectivity

Additional relevant MeSH terms:

Schizotypal Personality Disorder

Levodopa

Benserazide

Study Results

No Results Posted as of Nov 6, 2017