Trial Outcomes & Findings for Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia (NCT NCT03323437)

NCT ID: NCT03323437

Last Updated: 2024-05-06

Results Overview

Dorsal Caudate (DCA) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of GABA levels, over water, in the dorsal caudate. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 26 participants
• Primary outcome timeframe: Baseline and 4 weeks of treatment for patients, baseline for controls
• Results posted on: 2024-05-06

Participant Flow

Participant milestones

Measure	Patient Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control Healthy, psychosis-free controls who will not receive risperidone
Overall Study STARTED	13	13
Overall Study COMPLETED	13	9
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Measure	Patient Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control Healthy, psychosis-free controls who will not receive risperidone
Overall Study Withdrawal by Subject	0	4

Baseline Characteristics

Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

Baseline characteristics by cohort

Measure	Patient n=13 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=9 Participants Healthy, psychosis-free controls who will not receive risperidone	Total n=22 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	23.9 years STANDARD_DEVIATION 3.3 • n=5 Participants	26.4 years STANDARD_DEVIATION 2.7 • n=7 Participants	24.8 years STANDARD_DEVIATION 3.3 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 4 weeks of treatment for patients, baseline for controls

Population: The number of participants analyzed is lower than the participant flow as data from several subjects were excluded due to MRS quality control issues brought about by unreliable performance of a head coil.

Dorsal Caudate (DCA) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of GABA levels, over water, in the dorsal caudate. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Outcome measures

Measure	Patient n=10 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=8 Participants Healthy, psychosis-free controls who will not receive risperidone
Change in Biomarkers of Treatment Response: Dorsal Caudate (DCA) Gamma Amino Butyric Acid (GABA) Levels	-0.65 institutional units Interval -0.95 to -0.35	.0037 institutional units Interval 0.00333 to 0.004

PRIMARY outcome

Timeframe: Baseline and 4th week of treatment for patients, baseline only for controls

Population: The number of participants analyzed is lower than the participant flow as data from several subjects were excluded due to MRS quality control issues brought about by unreliable performance of a head coil.

Dorsal Caudate (DCA) Glx levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of the levels of Glx over water in the dorsal caudate. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Outcome measures

Measure	Patient n=10 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=8 Participants Healthy, psychosis-free controls who will not receive risperidone
Change in Biomarkers of Treatment Response: Dorsal Caudate (DCA) Glx (Glutamate+Glutamine)	-.28 institutional units Interval -0.8 to 0.24	.00221 institutional units Interval 0.00198 to 0.00244

PRIMARY outcome

Timeframe: Baseline and 4th week of treatment for patients, baseline only for controls

Population: The number of participants analyzed is lower than the participant flow as data from several subjects were excluded due to MRS quality control issues brought about by unreliable performance of a head coil.

Medial Prefrontal Cortex (MPFC) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of GABA levels, over water, in the mPFC. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Outcome measures

Measure	Patient n=10 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=8 Participants Healthy, psychosis-free controls who will not receive risperidone
Change in Biomarkers Reflecting Treatment Response: Medial Prefrontal Cortex (MPFC) Gamma Amino Butyric Acid (GABA)	.85 institutional units Interval 0.05 to 1.64	.00247 institutional units Interval 0.0022 to 0.0025

PRIMARY outcome

Timeframe: Baseline and 4th week of treatment for patients, baseline for controls

Population: The number of participants analyzed is lower than the participant flow as data from several subjects were excluded due to MRS quality control issues brought about by unreliable performance of a head coil.

Medial Prefrontal Cortex (MPFC) Glx levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of glx levels, over water, in the mPFC. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Outcome measures

Measure	Patient n=10 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=8 Participants Healthy, psychosis-free controls who will not receive risperidone
Change in Biomarkers Reflecting Treatment Response: Medial Prefrontal Cortex (MPFC) Glx (Glutamate+Glutamine)	0.19 institutional units Interval -0.54 to 0.93	.00191 institutional units Interval 0.00174 to 0.00208

SECONDARY outcome

Timeframe: Baseline and 4th week of of treatment for patients, baseline only for controls

Population: The number of participants analyzed is lower than the participant flow as some subjects did not finish all assessments in the MATRICS necessary to calculate this outcome.

Memory, attention, reasoning, emotional intelligence, and verbal ability will be assessed using the MCCB before and after 4 weeks of treatment. MATRICS Consensus Cognitive Battery (MCCB) as measure of Neurocognitive/Functional Measures is a standardized battery designed to measure cognitive functioning in people with schizophrenia. The MCCB is represented as a percentile score. This score can go from 0 to 100 where a higher score indicates a better performance. For patients this is a change measure. For control subjects, this is a one time measure.

Outcome measures

Measure	Patient n=8 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=8 Participants Healthy, psychosis-free controls who will not receive risperidone
Changes in Neurocognitive Performance: MATRICS Consensus Cognitive Battery (MCCB)	0.222 percentile score Interval 0.0 to 34.4	42.9 percentile score Interval 1.4 to 91.9

SECONDARY outcome

Timeframe: Baseline

Population: The number of participants analyzed is lower than the participant flow as some subjects did not complete this assessment.

The WAMI Score at Baseline is a measure of socioeconomic status across countries and culture. The index scale goes from 0 (lower socioeconomic situation) to 1 (highest socioeconomic situation).

Outcome measures

Measure	Patient n=7 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=5 Participants Healthy, psychosis-free controls who will not receive risperidone
WAMI (Wealth Asset and Income)	.901 score on a scale Standard Deviation .179	.982 score on a scale Standard Deviation .027

SECONDARY outcome

Timeframe: Baseline and week 4 for patients; for controls only baseline

Population: The number of participants analyzed is lower than the participant flow as some subjects were unable to complete all measures.

Changes in Positive and Negative Symptoms will be assessed across the treatment period using the PANSS.

Participants are rated on a scale of

1. (Absent)

2. (Minimal)

3. (Mild)

4. (Moderate)

5. (Moderate severe)

6. (Severe)

7. (Extreme)

to describe Positive, Negative and General symptomatology. Items from each subscale (Positive, Negative, and General) are summed for their respective scales, with lower numbers indicating less severe or absent symptomatology, and higher scores indicating more severe symptoms. A total sum of all subscales is also computed to reflect overall symptom severity.

Positive Subscale: 7 items, minimum score = 7, maximum score = 49 Negative Subscale: 7 items, minimum score = 7, maximum score = 49 General Subscale: '16 items, minimum score = 16, maximum score = 112 Total Score: 30 items, minimum score = 30, maximum score = 210.

For patients this is a change measure. For control subjects, this is a one time measure.

Outcome measures

Measure	Patient n=12 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=9 Participants Healthy, psychosis-free controls who will not receive risperidone
Changes in Clinical Symptomatology: Positive and Negative Syndrome Scale (PANSS)	-0.09 score on a scale Standard Deviation .15	31.89 score on a scale Standard Deviation 2.98

SECONDARY outcome

Timeframe: Baseline and week 4

Population: This measure is solely for patients and people who received antipsychotic treatment, so control subjects did not complete this measure.

Motor symptomatology associated with tardive dyskinesia (TD) assessed using the AIMS.

The measure consists of 10 items with scale/scores for each item of:

0 None

1. Minimal

2. Mild

3. Moderate

4. Severe Higher ratings = higher levels of motor symptoms which is worse. This scale assesses abnormal movements for parts of the body.

The total score is a sum score of items 1-10 and can be 0-40, with 40 being the most symptomatic (i.e., most extrapyramidal side effects, or worse).

Outcome measures

Measure	Patient n=13 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control Healthy, psychosis-free controls who will not receive risperidone
Changes in Motor Symptomatology: Abnormal Involuntary Movement Scale (AIMS)	-.077 score on a scale Standard Deviation .28	—

SECONDARY outcome

Timeframe: Baseline and week 4 for patients; for controls this is a baseline measure only

Population: The number of participants analyzed is lower than the participant flow as some subjects did not complete all measures.

Changes in clinical severity over the course of treatment will be monitored using the The Clinical Global Impression Scale (CGI) consists of two items.- Severity scale (CGI-S).

Severity - The first item assesses the patient's current level of mental health symptomatology compared to the clinician's experience with other patients with the same diagnosis. The scale ranges from

1. (Normal, not at all ill)

2. (Borderline mentally ill)

3. (Mildly ill)

4. (Moderately ill)

5. (Markedly ill)

6. (Severely ill)

7. (Among the most extremely ill patients)

Improvement - The second item assesses how much the patient's symptomatology has changed since the last clinical visit.

1. Very much improved

2. Much improved

3. Minimally improved

4. No change

5. Minimally worse

6. Much worse

7. Very much worse

For patients this is a change measure. For control subjects, this is a one time measure.

The possible score range is 1-7 with 1 being least and 7 being most symptomatic.

Outcome measures

Measure	Patient n=13 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=9 Participants Healthy, psychosis-free controls who will not receive risperidone
Changes in Clinical Severity: Clinical Global Impression Scale	-0.054 score on a scale Standard Deviation .10	1 score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and week 4 for patients; for controls only baseline

Population: The number of participants analyzed is lower than the participant flow as some subjects did not complete this measure.

Changes in global functioning over the course of treatment will be assessed using the Global Assessment of Functioning (GAF).

Participants are rated 1-100 on their level of functioning, according to clinical observation:

91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 If symptoms are present, they expected reactions to stressors 61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Impairment in reality testing or communication or major impairment in several areas 21-30 Behavior influenced by delusions or hallucinations or serious impairment in communication/judgment/inability to function in almost all areas 11-20 Some danger of hurting self or others or occasionally fails to maintain minimal personal hygiene or gross impairment in communication 1-10 Persistent violence risk or lack of self-care 0 No info

For patients this is a change measure. For control subjects, this is a one time measure.

Outcome measures

Measure	Patient n=12 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=9 Participants Healthy, psychosis-free controls who will not receive risperidone
Changes in Global Functioning: Global Assessment of Functioning (GAF)	0.21 score on a scale Standard Deviation .20	86.4 score on a scale Standard Deviation 8.53

SECONDARY outcome

Timeframe: This measure is administered on Day 1 of the study.

Population: The number of participants analyzed is lower than the participant flow as some subjects did not complete all measures.

This measure is a self-reported questionnaire which assesses for any use of the following substances within the past month prior to the initial research visit Tobacco (if the respondent indicates that they have used tobacco in the past month, they are additionally asked, "On average, how many cigarettes per day have you smoked in the past 7 days?" Alcohol, Cocaine, Marijuana, Opiates, Amphetamines, phencyclidine (PCP) Other Drugs of Abuse (if the respondent indicates they have used other drugs of abuse within the past month of the initial research visit, they are given the opportunity to "specify" which other drugs of abuse they used

Outcome measures

Measure	Patient n=10 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=9 Participants Healthy, psychosis-free controls who will not receive risperidone
Recreational Substances Used by Patients as Recorded by the Substance Use Questionnaire	6 Participants	4 Participants

SECONDARY outcome

Timeframe: This measure is completed on Day 1 of the study.

Population: The number of participants analyzed is lower than the participant flow as some subjects did not complete all measures.

This measure assesses a participant's verbal ability to determine whether they are cognitively able to complete the measures involved in the study. The participant will read from a list of 50 English words and the rater will record whether the pronunciation was correct on a score card for each word spoken. A standard score below the 70th percentile on this measure is indicative of an intellectual disability which would exclude a participant from being clinically and cognitively eligible to complete this study. The potential score range is 0-50. A higher score indicates better cognitive ability. There is only one total score.

Outcome measures

Measure	Patient n=14 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=9 Participants Healthy, psychosis-free controls who will not receive risperidone
Participants' Verbal I.Q (Intelligence Quotient) as Assessed by the WTAR (Wechsler Test of Adult Reading) to Determine Clinical Eligibility	36.9 score on a scale Standard Deviation 8.43	43.9 score on a scale Standard Deviation 6.23

SECONDARY outcome

Timeframe: This measure is completed on Day 1 of the study.

Population: The number of participants analyzed is lower than the participant flow as some subjects did not complete all measures.

This measure assesses a participant's preference regarding which hand they would use to complete a specific task. They have the option to indicate whether they would use they would always or most of the time use their left, right, or both left and right hands to complete each task. This measure assesses handedness based on the amount of responses which indicate the participant is either left handed, right handed, or ambidextrous. Below we specifically report on the number of individuals who were predominantly right handed.

Outcome measures

Measure	Patient n=13 Participants Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=9 Participants Healthy, psychosis-free controls who will not receive risperidone
Participants' Self-Reported Handedness as Recorded by the Edinburgh Handedness Scale (Predominantly Right)	11 Participants	7 Participants

Adverse Events

Patient

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Patient n=13 participants at risk Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone Risperidone: Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.	Control n=13 participants at risk Healthy, psychosis-free controls who will not receive risperidone
Nervous system disorders Headache	7.7% 1/13 • Number of events 1 • 4-6 weeks for patients, 1-2 weeks for controls	0.00% 0/13 • 4-6 weeks for patients, 1-2 weeks for controls
Musculoskeletal and connective tissue disorders restlessness	7.7% 1/13 • Number of events 1 • 4-6 weeks for patients, 1-2 weeks for controls	0.00% 0/13 • 4-6 weeks for patients, 1-2 weeks for controls
Nervous system disorders drowsiness/sedation	61.5% 8/13 • Number of events 10 • 4-6 weeks for patients, 1-2 weeks for controls	0.00% 0/13 • 4-6 weeks for patients, 1-2 weeks for controls
Musculoskeletal and connective tissue disorders involuntary movements	23.1% 3/13 • Number of events 3 • 4-6 weeks for patients, 1-2 weeks for controls	0.00% 0/13 • 4-6 weeks for patients, 1-2 weeks for controls

Additional Information

Dr. Dikoma C. Shungu

Weill Cornell Medicine

Phone: 212-746-2481

Email: dcs7001@med.cornell.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place