Clinical trial NCT03781115: Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia
Official title: Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Schizophrenia
Keywords: schizophrenia, psychosis, ziprasidone, olanzapine
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: Sidney R. Baer, Jr. Foundation
First posted: 2018-12-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators will first conduct a dose-response evaluation of the anti-psychotic drug ziprasidone (Geodon) (20, 40, or 60 mg tablet) or olanzapine (Zyprexa®) (2.5, 5, 7.5, or 10 mg tablet) in non-psychiatric ill control individuals to determine the dosage that promotes sedation in individuals versus a placebo. The evaluation will comprise a physical examination, drug/pregnancy screenings and sleepiness questionnaires. Once the dosage of the anti-psychotic medication is determined new healthy subjects will be recruited to ingest the medication and have an electroencephalogram (EEG) recording taken. If the dosage of medication does not show an effect on the EEG the investigators will ask the individual to come back on a different day so the next higher dose of medication can be given. Once a the healthy subject's EEG shows an effect new control subjects and individuals with a diagnosis of schizophrenia will be recruited.
Primary purpose: DIAGNOSTIC

Brief summary: Schizophrenia is a severe psychotic illness of unknown cause that affects 1% of the population worldwide. Currently, there is no diagnostic test for schizophrenia. Instead, the diagnosis is typically established through a psychiatric interview of the patient, who is evaluated against a set of established criteria of signs and symptoms. It can take many months to years to establish a diagnosis of schizophrenia and achieve an appropriate treatment regimen to attain resolution of the patient's symptoms. This process is particularly challenging in areas of limited access to specialists a problem not only in third world countries and rural regions, but throughout the United States where there can be long waits to obtain an appointment with a psychiatrist. The present research experiment investigates a potential novel method for diagnosing schizophrenia.

The overall objective of the study is to test the hypothesis that patients with schizophrenia will have a heightened tolerance to the sedating effects of anti-psychotic medications, which will be reflected in differences in their electroencephalogram (EEG) when compared to healthy normal controls. The investigators expect that the schizophrenia patients will score on the "more alert" and "less sleepy" ends of these scales, and that the normal control subjects will show the opposite response. A patient that fails to become sedated or experience the sleepiness side effects, typically caused by the anti-psychotic medication, may support the existing diagnosis of schizophrenia. Measures of the subjects' level of sedation that are found to correlate significantly with EEG response and diagnosis will be used to create a diagnostic test. This simple and inexpensive test will consist of a single dosage of anti-psychotic medication, and a rapid assessment tool with scores that have a high degree of predictive validity for the diagnosis of schizophrenia.

Detailed description: The overall objective of the study is to test the hypothesis that patients with schizophrenia will have a heightened tolerance to the sedating effects of antipsychotic medications, which will be reflected in differences in the participants' electroencephalogram response (EEG), when compared to healthy control participants.The following Specific Aims are designed to test this hypothesis and create the diagnostic tool.

Specific Aim 1: The investigators will first conduct a pilot dose-response evaluation of the anti-psychotic drugs ziprasidone (Geodon) (20, 40, or 60 mg tablet) and olanzapine (Zyprexa®) (2.5, 5, 7.5, or 10 mg tablet) in non-psychiatric ill control participants to determine the optimal dosage that promotes sedation in healthy participants versus a placebo. The evaluation will comprise a physical examination and questionnaires. The investigators will start with the lowest dose of each drug and if the dosage fails to induce sedation in healthy participants, the investigators will repeat the pilot dose-response evaluation with the next higher dose until the maximum dose is reached for both drugs. Specific Aim 2. To determine whether the pattern of EEG activity in response to a single dose of the anti-psychotic medication determined from the dose-response study from Aim 1 distinguishes schizophrenia participants from normal controls. The investigators will start with 2-4 healthy control participants to determine that the results show a discernible effect on the EEG using the dosage from Aim 1. If the dose of anti-psychotic medication fails to show an effect on the EEG the investigators will increase the dosage until the maximum dosage of the chosen medication is used. Once the dosage is identified the investigators will move onto getting IRB approval to evaluate participants diagnosed with schizophrenia.

Eligibility criteria: Inclusion Criteria Healthy Control

1. Be between 18 and 40 years of age
2. Be able to understand English
3. Have no history of psychosis
4. Have no history of sleep apnea, heart condition or seizure
5. Have no known drug allergies
6. The ability to swallow a pill

Exclusion Criteria Healthy control

1. Refuse to sign the consent form
2. Drink caffeine or alcohol within 24 hours of the study
3. Have the EKG readout report borderline or abnormal ECG
4. Have the 12 panel urine drug screen show a positive result
5. Be pregnant

Inclusion Criteria Schizophrenic subject

1. Be between 18 and 40 years of age
2. Be able to understand English
3. Have been diagnosed with a Schizophrenia Spectrum or other psychotic disorder
4. Belong to one of three groups:

   1. Never medicated patients with a first episode of psychosis
   2. Have not received long acting injectable (depot) antipsychotic in previous 6 months
   3. Have not received oral antipsychotic (or antidepressant that has serotonergic action) in previous 2 weeks
5. Have no history of sleep apnea, heart condition or seizure
6. Have no known drug allergies
7. Be able to swallow a pill
8. Healthy as determined by the enrolling physician(s)

Exclusion Criteria Schizophrenic subject

1. Refuse to sign the consent form
2. Drink caffeine or alcohol within 24 hours of the study
3. Have the EKG readout report borderline or abnormal ECG
4. Have the 12 panel urine drug screen show a positive result
5. Be pregnant

Primary outcomes:
measure: Heart Rate
timeFrame: up to 2 years
measure: Pulse Rate
timeFrame: up to 2 years
measure: Stanford Sleepiness Scale
timeFrame: up to 2 years
measure: Epworth Sleepiness Scale
timeFrame: up to 2 years
measure: Fatigue Severity Scale
timeFrame: up to 2 years
measure: Chalder Fatigue Scale
timeFrame: up to 2 years
measure: Psychomotor physical computerized test
timeFrame: up to 2 years
measure: Hand Fatigue Scale
timeFrame: up to 2 years
measure: Electroencephalogram
timeFrame: up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
Study officials:
affiliation: University of Arizona College of Medicine
name: Amelia Gallitano, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Everson G, Lasseter KC, Anderson KE, Bauer LA, Carithens RL Jr, Wilner KD, Johnson A, Anziano RJ, Smolarek TA, Turncliff RZ. The pharmacokinetics of ziprasidone in subjects with normal and impaired hepatic function. Br J Clin Pharmacol. 2000;49 Suppl 1(Suppl 1):21S-26S. doi: 10.1046/j.1365-2125.2000.00149.x.
citation: Albaugh VL, Singareddy R, Mauger D, Lynch CJ. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers. PLoS One. 2011;6(8):e22662. doi: 10.1371/journal.pone.0022662. Epub 2011 Aug 9.