Trial Outcomes & Findings for Evaluating Isradipine for Cognitive Enhancement in Schizophrenia and Schizoaffective Disorder (NCT NCT01658150)

Results Overview

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 composite T score. A t score is a type of standard score computed by multiplying a z-score (how many standard deviations an element is from the mean) by 10 and adding 50.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

11 participants

Primary outcome timeframe

baseline and week 4

Results posted on

2018-12-05

Participant Flow

Participant milestones

Participant milestones
Measure	Isradipine Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Overall Study STARTED	11
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Isradipine Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Evaluating Isradipine for Cognitive Enhancement in Schizophrenia and Schizoaffective Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Isradipine n=11 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Age, Continuous	37.5 years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and week 4

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 composite T score. A t score is a type of standard score computed by multiplying a z-score (how many standard deviations an element is from the mean) by 10 and adding 50.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
MATRICS Consensus Cognitive Battery (MCCB) Change in Neurocognitive/Functional Measures Week 4	38.2 z-score Standard Deviation 12.6
MATRICS Consensus Cognitive Battery (MCCB) Change in Neurocognitive/Functional Measures Baseline	39.8 z-score Standard Deviation 13.2

PRIMARY outcome

Timeframe: baseline and week 4

UCSD Performance Skills Assessment (UPSA) - The UPSA is performance-based measure of real-world daily functioning abilities. Participants receive scores for the communication subscale (range = 0-20), with higher score indicating better neurocognitive functioning

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
UPSA Communication Score baseline	15.3 score on a scale Standard Deviation 2.8
UPSA Communication Score week 4	16.5 score on a scale Standard Deviation 2.0

PRIMARY outcome

Timeframe: baseline and Week 4

The QoL is a measure of the perceived satisfaction in an individual's daily life. This 16-item self-report measure is rated on a 7-point scale, ranging from 1 (terrible) to 7 (delighted), with a total score range from 16-112, where higher scores indicate higher satisfaction with daily life.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Quality of Life (QoL) Scale Baseline	96.5 score on a scale Standard Deviation 15.5
Quality of Life (QoL) Scale Week 4	93.0 score on a scale Standard Deviation 16.9

SECONDARY outcome

Timeframe: up to 4 weeks

The PRISE is a physician-administered checklist of adverse events. PRISE contains 33 items, each defined by an adverse event. Each item is rated on a 3-point scale, ranging from 0 (not present) to 2 (distressing), with a total score range from 0-66, where higher scores indicate more adverse events. Mean change for adverse events at week 4 as compared to baseline

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Mean Change in PRISE Adverse Event Checklist Score	-0.7 score on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: baseline and week 4

Number of participants with normal ECG readings to confirm inclusion into study and compared at week 4 to baseline

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Number of Participants With Normal ECG Baseline	10 Participants
Number of Participants With Normal ECG Week 4	10 Participants

SECONDARY outcome

Timeframe: baseline and week 4

Number of participants with normal chemistry panel to confirm inclusion into study at baseline and week

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Number of Participants With Normal Chemistry Panel Baseline	10 Participants
Number of Participants With Normal Chemistry Panel Week 4	10 Participants

SECONDARY outcome

Timeframe: baseline and week 4

Number of participants with normal CBC to confirm inclusion into study at baseline and week 4

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Number of Participants With Normal Complete Blood Count (CBC) Baseline	10 Participants
Number of Participants With Normal Complete Blood Count (CBC) Week 4	10 Participants

SECONDARY outcome

Timeframe: baseline and Week 4

Mean change for abnormal involuntary movements throughout the study. The AIMS is a physician-administered scale of abnormal involuntary movements. AIMS consists of 10 items, each defined by a series of movements. Each item is rated on a 5-point scale, ranging from 0 (not observed) to 4 (severe), with a total score range from 0-40, where higher scores indicate abnormal involuntary movements.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Abnormal Involuntary Movement Scale (AIMS)	0.7 score on a scale Standard Deviation 2.9

SECONDARY outcome

Timeframe: baseline and week 4

Mean change for drug-induced disordered movement throughout the study. The MSAS is a physician-administered scale of abnormal drug-induced movements. MSAS consists of 6 items, each defined by a series of movements. Each item is rated on a 5-point scale, ranging form 0 (not observed) to 4 (most severe), with a total range of 0-24, where higher scores indicate drug-induced disordered movement.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Modified Simpson Angus Scale (MSAS)	-0.3 score on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: up to 4 weeks

Population: Data not collected.

a 21-question multiple choice, self-report inventory that is used for measuring the severity of suicidal ideation. Scoring is from a 0 (not at all) to 3 (severe) with a total score range of 0-63. Higher total scores indicate more severe suicidal ideation symptoms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 4 weeks

Number of participants with Suicidal acknowledgements based on the Columbia Suicide Severity Rating Scales (C-SSRS) - Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Number of Participants With Suicidal Acknowledgments	0 Participants

SECONDARY outcome

Timeframe: baseline

Number of participants with confirm diagnosis for inclusion into study using the Structured Clinical Interview for the DSM-IV (SCID-IV)

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Number of Participants With a Confirmed SCID-IV	10 Participants

SECONDARY outcome

Timeframe: up to 4 weeks

Mean change for positive symptoms throughout the study. BPRS consists of 18 items, each defined by a series of symptoms. Each item is rated on a 7-point scale, ranging from 1 (not observed) to 7 (very severe), with a total score range from 18-126, where higher scores indicate psychiatric symptoms.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Brief Psychiatric Rating Scale (BPRS)	-1.0 score on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: up to 4 weeks

Mean change of negative symptoms throughout the study. SANS consists of 22 items, each defined by a series of symptoms. Each item is rated on a 6-point scale, ranging from 0 (no presence) to 5 (severe presence), with a total range of 0-110, where higher scores indicate negative symptoms.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Scale for the Assessment of Negative Symptoms (SANS)	-1.6 score on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: up to 4 weeks

Mean change of symptoms of depression throughout the study. HRSD consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe), with a total score range of 0-56, where higher score indicates more depressive symptoms

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Hamilton Rating Scale for Depression (HRSD)	-0.6 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: up to 4 weeks

Mean change of clinical impression of severity of psychiatric illness throughout the study. CGI consists of one item, defined by severity of illness. It is rated on a 7-point scale, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients), with a total range score of 1-7, where higher score indicates severity of illness.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Clinical Global Impression Scale (CGI)	-0.2 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: up to 4 weeks

Mean change of symptoms of mania throughout the study. CARS-M contains 14 items rated from 0 (absent) to 5 (present) and one item scored 0 to 4, with total range from 0 to 74, where higher score indicates manic symptoms.

Outcome measures

Outcome measures
Measure	Isradipine n=10 Participants Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. Isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Clinician Administered Rating Scale for Mania (CARS-M)	0 score on a scale Standard Deviation 0.7

Adverse Events

Isradipine

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Isradipine n=11 participants at risk Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. isradipine as utilized in this trial will be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be tolerated, the subject will be discontinued.
Gastrointestinal disorders Nausea	9.1% 1/11 • 4 weeks
General disorders Dizziness	9.1% 1/11 • 4 weeks
Skin and subcutaneous tissue disorders Dry skin	9.1% 1/11 • 4 weeks
General disorders Poor coordination	9.1% 1/11 • 4 weeks
Eye disorders Blurred vision	9.1% 1/11 • 4 weeks
Ear and labyrinth disorders Tinnitus	27.3% 3/11 • 4 weeks
Renal and urinary disorders Frequent urination	27.3% 3/11 • 4 weeks
Reproductive system and breast disorders Menstrual irregular	54.5% 6/11 • 4 weeks
General disorders Difficulty sleeping	36.4% 4/11 • 4 weeks
General disorders Hypersomnia	9.1% 1/11 • 4 weeks
Reproductive system and breast disorders Loss of libido	9.1% 1/11 • 4 weeks
Psychiatric disorders Anxiety	36.4% 4/11 • 4 weeks
General disorders Poor concentration	27.3% 3/11 • 4 weeks
General disorders Restlessness	18.2% 2/11 • 4 weeks
General disorders Fatigue	27.3% 3/11 • 4 weeks
General disorders Decreased energy	27.3% 3/11 • 4 weeks

Additional Information

Dr. Katherine Burdick

Icahn School of Medicine at Mount Sinia

Phone: 212-659-8841

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place