Biomarkers in First Episode Schizophrenia

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT02033382
• Collaborator: (none)
• Enrollment: 165
• Location: 1
• Duration (Months): 29
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

This study will identify and evaluate relevant biomarkers and structural brain imaging for understanding potential biological illness related mechanisms in medication-naïve subjects with early psychosis before and after initiation of antipsychotic medication

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizophreniform Disorder; Schizoaffective Disorder, Depressed Type

Detailed Description

It is currently unknown whether deterioration early in the course of psychotic illness represents medication toxicity or the natural course of the illness. The study will help clarify this issue in observing 70 schizophrenic patients before and after they are prescribed an antipsychotic via standard of care.

In addition, schizophrenia is a heterogeneous disorder and a putative brain-derived neurotrophic factor (BDNF) deficit, while possibly a common pathway, may not fully capture the biological diversity-the supplemental biomarkers will allow us to perform a more comprehensive assessment of factors contributing to clinical course. Taken together analysis of these biomarkers in relation to clinical course and in relation to healthy subjects will inform us about biological mechanisms contributing to illness onset, effects of antipsychotic medication on these mechanisms, and the predictive value of the biomarkers for clinical course. This information will provide the foundation for future early intervention trials targeting biological mechanisms utilizing a personalized medicine approach.

The baseline visit for 70 schizophrenic patients and 70 healthy age and gender matched controls consists of structural and functional MRI in addition to a blood draw for biomarkers including BDNF, inflammation markers, DNA, oxidative stress, and folate status and additionally a salivary cortisol sample collection. Biomarkers and imaging will be repeated after 8 weeks of antipsychotic treatment in patients.

Study Design

• Study Type: Observational
• Actual Enrollment: 165 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Biomarkers in First Episode Schizophrenia
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Healthy Controls Age and gender matched healthy controls
Patients Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.

Outcome Measures

Primary Outcome Measures

1. Biomarkers [Baseline]

   Compare biomarkers for inflammation, BDNF, oxidative stress, glucocorticoids and folate/methylation status in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.

2. Salivary Cortisol Levels [Baseline and week 8]

   Compare biomarkers at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.

3. Salivary Cortisol Levels [Baseline]

   Compare biomarkers for stress (salivary cortisol) in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.

4. Change in Salivary Cortisol Levels [Baseline and week 8]

   Compare salivary cortisol at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.

Secondary Outcome Measures

1. Left Hippocampal Volumetric Integrity (HVI) [Baseline]

   Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline hippocampal volume.

2. Cognitive Performance [Baseline, week 8]

   Compare cognitive performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in medication- naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline cognitive performance. The composite score on the MCCB is calculated by the software using all tests administered. The composite score is a t-score assuming the mean score (50%) is the normative performance of the general population. The composite score ranges from 0-100 with a standard deviation of 10. A score greater than 50 implies a score better than the average population norm and a score less than 50 indicates performance worse than the general population norm. For schizophrenia subjects who complete 8 weeks of antipsychotic treatment, week 8 MATRICS testing results will be used to minimize the effect of psychosis on cognitive performance.

3. Annualized Change in Left Hippocampal Volume Integrity [Baseline, week 8]

   Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects before and after 8 weeks treatment with antipsychotic to assess evidence for early neurotoxicity. This outcome measure reports annualized rate of change in Left Hippocampal Volume Integrity (LHVI) because a few participants had a delay in their week 8 visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male or female

2. Ages 15-40 years

3. Schizophrenia, any subtype or Schizophreniform disorder

4. Sufficient proficiency in English or Spanish to complete assessments (US)

Exclusion Criteria:

1. Major depression by the Diagnostic and Statistical Manual of Mental Disorders IV criteria

2. Calgary Depression Scale for Schizophrenia (CDSS) score of 7 or greater.

3. Clinical Global Assessment of Severity of Suicidality of 3 (moderate) or greater.

4. Serious suicide attempt within three years

5. Treatment with an antipsychotic or antidepressant within the last six months

6. Active alcohol or other substance abuse or dependence within one month

7. Unstable medical illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bellevue Hospital	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT02033382
• Other Study ID Numbers: 12-02903
• First Posted: Jan 10, 2014
• Last Update Posted: Jan 14, 2021
• Last Verified: Jan 1, 2021

• Additional relevant MeSH terms: Disease; Schizophrenia; Psychotic Disorders

Study Results

Participant Flow

Arm/Group Title	Healthy Controls	Patients
Arm/Group Description	Age and gender matched healthy controls	Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.
Period Title: Overall Study
STARTED	83	82
COMPLETED	32	36
NOT COMPLETED	51	46

Baseline Characteristics

Arm/Group Title	Healthy Controls	Patients	Total
Arm/Group Description	Age and gender matched healthy controls	Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.	Total of all reporting groups
Overall Participants	73	79	152
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.86 (6.40)	25.19 (7.39)	24.56 (6.95)
Sex: Female, Male (Count of Participants)
Female	40 54.8%	40 50.6%	80 52.6%
Male	33 45.2%	39 49.4%	72 47.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	73 100%	74 93.7%	147 96.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	3 3.8%	3 2%
White	0 0%	2 2.5%	2 1.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
China	73 100%	79 100%	152 100%

Outcome Measures

1. Primary Outcome

Title	Biomarkers
Description	Compare biomarkers for inflammation, BDNF, oxidative stress, glucocorticoids and folate/methylation status in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Not all biomarkers were available for analysis for all subjects.

Arm/Group Title	Healthy Controls	Patients
Arm/Group Description	Age and gender matched healthy controls	Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.
Measure Participants	62	69
BDNF	287.37	340.83
Thioredoxin	492.33	420.17
S100B	130.44	125.13
C-Reactive Protein	7610.07	7631.41
Interleukin 1B	76.77	68.82
Interleukin 8	63.41	71.30
Tumor Necrosis Factor	92.03	93.60
Interferon gamma	88.96	89.42
Glutamate	105.00	111.00
Aspartate	102.32	134.32
Homocysteine	4.79	4.83
Lactate	13.28	15.08

2. Primary Outcome

Title	Salivary Cortisol Levels
Description	Compare biomarkers at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.
Time Frame	Baseline and week 8

Outcome Measure Data

Analysis Population Description

Analysis was done for first episode participants who completed both Baseline and Week 8 only.

Arm/Group Title	Baseline	Week 8
Arm/Group Description	Biomarkers at baseline prior to risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects.	Biomarkers at week 8 of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects.
Measure Participants	29	29
C-reactive protein	7541.41	7627.60
Interleukin 1B	68.81	57.01
Interleukin 8	74.34	65.79
Interferon gamma	95.26	98.14
Tumor necrosis factor	93.60	89.45
Aspartate	3.71	4.75
Glutamate	5.21	5.29
Lactate	4.49	3.95
Homocysteine	4.78	5.02
BDNF	465.98	356.20
Thioredoxin	417.50	405.33
S100B	154.63	111.39

3. Primary Outcome

Title	Salivary Cortisol Levels
Description	Compare biomarkers for stress (salivary cortisol) in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	Patients
Arm/Group Description	Age and gender matched healthy controls	Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.
Measure Participants	54	46
Median (Inter-Quartile Range) [µg/dL]	4.88	6.56

4. Primary Outcome

Title	Change in Salivary Cortisol Levels
Description	Compare salivary cortisol at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.
Time Frame	Baseline and week 8

Outcome Measure Data

Analysis Population Description

Analysis was done for first episode subjects who completed both Baseline and Week 8 only.

Arm/Group Title	Baseline	Week 8
Arm/Group Description	salivary cortisol at baseline prior to risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects.	salivary cortisol at week 8 of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects.
Measure Participants	19	19
Median (Inter-Quartile Range) [µg/dL]	7.41	4.36

5. Secondary Outcome

Title	Left Hippocampal Volumetric Integrity (HVI)
Description	Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline hippocampal volume.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	Patients
Arm/Group Description	Age and gender matched healthy controls	Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.
Measure Participants	54	57
Median (Inter-Quartile Range) [% of hippocampal volumetric integrity]	.9512	.9275

6. Secondary Outcome

Title	Cognitive Performance
Description	Compare cognitive performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in medication- naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline cognitive performance. The composite score on the MCCB is calculated by the software using all tests administered. The composite score is a t-score assuming the mean score (50%) is the normative performance of the general population. The composite score ranges from 0-100 with a standard deviation of 10. A score greater than 50 implies a score better than the average population norm and a score less than 50 indicates performance worse than the general population norm. For schizophrenia subjects who complete 8 weeks of antipsychotic treatment, week 8 MATRICS testing results will be used to minimize the effect of psychosis on cognitive performance.
Time Frame	Baseline, week 8

Outcome Measure Data

Analysis Population Description

Data provided only for subjects who completed assessments at both time points.

Arm/Group Title	Healthy Controls	Patients
Arm/Group Description	Age and gender matched healthy controls	Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.
Measure Participants	36	30
Baseline MCCB Composite Score	47.50	34
Week 8 MCCB Composite Score	49.50	42.50

7. Secondary Outcome

Title	Annualized Change in Left Hippocampal Volume Integrity
Description	Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects before and after 8 weeks treatment with antipsychotic to assess evidence for early neurotoxicity. This outcome measure reports annualized rate of change in Left Hippocampal Volume Integrity (LHVI) because a few participants had a delay in their week 8 visit.
Time Frame	Baseline, week 8

Outcome Measure Data

Analysis Population Description

This analysis includes participants that completed both baseline and week 8 visits.

Arm/Group Title	Healthy Controls	Patients
Arm/Group Description	Age and gender matched healthy controls	Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.
Measure Participants	31	24
Median (Inter-Quartile Range) [Percentage of standard hippocampal vol.]	0.004535	-0.03027

Adverse Events

Arm/Group Title	Healthy Controls		Patients
Arm/Group Description	Age and gender matched healthy controls		Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.
All Cause Mortality
	Healthy Controls		Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Healthy Controls		Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		0/79 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Controls		Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		1/79 (1.3%)
Cardiac disorders
Hypertension	0/73 (0%)	0	1/79 (1.3%)	1
Eye disorders
Blurred Vision	0/73 (0%)	0	1/79 (1.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.