The Sub-Sero Study

NCT ID: NCT03994965

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-01

Study Completion Date

2024-12-04

Brief Summary

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Schizophrenia is a severe, often chronic mental disorder, characterized by positive and negative symptoms and cognitive deficits. The serotonin hypothesis of schizophrenia was proposed in the 1950s, but only recently, pimavanserin, the first antipsychotic medication with selective affinity for the serotonin 2A receptor was approved.

The aim of this translational proposal is to test the clinical validity of the serotonin hypothesis of schizophrenia and to guide development of operational, objective criteria for stratification of first-episode schizophrenia spectrum patients before antipsychotic treatment.

Our previous data have strongly suggested, that a subgroup of antipsychotic-naïve patients will respond to serotonin 2A receptor (2AR) blockade. This treatment will cause minimal side-effects compared with conventional dopamine D2/3 receptor blockade.

In this Danish, investigator-initiated trial, we will establish a cohort of 40 antipsychotic-free, first-episode schizophrenia spectrum patients and enrol them in a 6-week open label, one-armed trial with selective serotonin 2AR blockade (pimavanserin).

Before initiation of pimavanserin patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR binding potential using the radioligand \[¹¹C\]Cimbi-36; magnetic resonance spectroscopy (MRS) of cerebral glutamate levels; structural Magnetic Resonance imaging (MRI), including Diffusion Tensor Imaging (DTI); cognitive and psychopathological examinations; Electrocardiography (ECG), and blood sampling for genetic- and metabolic analyses.

Matched healthy controls will undergo parallel examinations, but not medical treatment and PET .

ACADIA Pharmaceuticals Inc. provides the study medication (pimavanserin). ACADIA had no influence on study design and will not take part in data processing or publication of the results of the study.

Detailed Description

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(More information will follow on study approval).

Conditions

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Schizophrenia Psychosis

Keywords

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Pimavanserin serotonin 2AR MR PET

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Proof-of-principle study, investigator initiated, open label study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Patients

40 antipsychotic-free, first-episode schizophrenia spectrum patients will receive 6 weeks of treatment with a selective serotonin 2A Receptor (2AR) blockade.

Before initiation of treatment patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR binding potential using the radioligand \[¹¹C\]Cimbi-36; magnetic resonance spectroscopy (MRS) of cerebral glutamate levels; structural Magnetic Resonance Imaging (MRI), including diffusion tensor imaging (DTI); cognitive and psychopathological examinations; Electrocardiography (ECG), and blood sampling for genetic- and metabolic analyses.

(Full description will be updated on approval).

Group Type EXPERIMENTAL

Pimavanserin 34 milligrams (MG) [Nuplazid]

Intervention Type DRUG

Daily treatment with 34 mg per os for 6 weeks. Followed by a wash-out period up to 14 days, do to the theoretical risk of corrected QT interval (QTc) prolongation. Conventional anti-psychotic treatment will be initiated only upon normal ECG.

Interventions

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Pimavanserin 34 milligrams (MG) [Nuplazid]

Daily treatment with 34 mg per os for 6 weeks. Followed by a wash-out period up to 14 days, do to the theoretical risk of corrected QT interval (QTc) prolongation. Conventional anti-psychotic treatment will be initiated only upon normal ECG.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Matched with patients on age (+/- 2 years), sex and parental socioeconomic status
* Age 18-45 years
* Legally competent (In Danish: 'myndige og habile i retslig forstand')
* Recruitment: through online advertisement (www.forsøgsperson.dk)

Exclusion Criteria

* Fulfilling the diagnostic criteria of schizophrenia, persistent delusional disorder, acute and transient psychotic disorders, schizoaffective disorder, other non-organic psychotic disorders and unspecified non-organic disorders (ICD-10: F20.x; F22.x; F23.x; F24.x; F25.x; F28; F29); verified by The Schedules for Clinical Assessment in Neuropsychiatry (SCAN) 2.0 interview (Wing et al. 1990)
* Age: 18-45 years
* Legally competent (In Danish: 'myndige og habile i retslig forstand')


* Prior use of antipsychotic medication longer than an episode of two weeks in the previous year and/or 6 weeks lifetime, and/or antipsychotic treatment within 30 days prior to inclusion.
* Current substance abuse ICD-10 (F1x.2) or substance abuse in any period up to 3 months prior to referral (exception: tobacco/nicotine, F17.2)
* Head injury with more than 5 minutes of unconsciousness
* Any coercive measure
* Metal implanted by operation
* Pacemaker
* Pregnancy (assessed by urine human chorionic gonadotropin (HCG))
* Female patients: Unwillingness to use safe contraception (Intra Uterine Device/System or hormonal contraceptives) during the study period including the wash out period.
* Severe physical illness
* Known QT prolongation or congenital prolongation of the QT interval
* Medical history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia
* Current treatment with drugs known to prolong QT interval including: Class 1A antiarrhythmics (e.g., quinidine, procainamide); Class 3 antiarrhythmics (e.g., amiodarone, sotalol); certain antibiotics (e.g., gatifloxacin, moxifloxacin).
* Allergies to any of the inactive ingredients and film coat components: pregelatinized starch, magnesium stearate, microcrystalline cellulose, hypromellose, talc, titanium dioxide, polyethylene glycol, and saccharin sodium.


* Any psychiatric illness any first-degree relatives with known psychiatric diagnoses or physical disease
* Substance abuse during the past 3 months or positive urine-screening of illegal drugs
* Head injury with more than 5 minutes of unconsciousness
* Components of metal implanted by operation
* Pacemaker
* Pregnancy (assessed by urine HCG)
* Severe physical illness
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rigshospitalet, Denmark

OTHER

Sponsor Role collaborator

GCP unit, Copenhagen University Hospital

UNKNOWN

Sponsor Role collaborator

ACADIA Pharmaceuticals Inc.

INDUSTRY

Sponsor Role collaborator

Bjorn H. Ebdrup

OTHER

Sponsor Role lead

Responsible Party

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Bjorn H. Ebdrup

MD PhD, associate professor, vice-chair of research CNSR

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Bjørn H Ebdrup, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Copenhagen

References

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Baltzersen OB, Meltzer HY, Frokjaer VG, Raghava JM, Baandrup L, Fagerlund B, Larsson HBW, Fibiger HC, Glenthoj BY, Knudsen GM, Ebdrup BH. Identification of a Serotonin 2A Receptor Subtype of Schizophrenia Spectrum Disorders With Pimavanserin: The Sub-Sero Proof-of-Concept Trial Protocol. Front Pharmacol. 2020 Apr 30;11:591. doi: 10.3389/fphar.2020.00591. eCollection 2020.

Reference Type DERIVED
PMID: 32425802 (View on PubMed)

Other Identifiers

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2019-001722-10

Identifier Type: -

Identifier Source: org_study_id