Effect of Single Dose Intranasal Insulin On Cognitive Function

Effect of Single Dose Intranasal Insulin on Cognitive Function in Patients With Schizophrenia

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00646581

Enrollment

Registered

2008-03-28

Start date

2006-10-31

Completion date

2010-01-31

Last updated

2013-02-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizoaffective Disorder, Schizophrenia

Keywords

Schizophrenia, Memory, Concentration, Insulin

Brief summary

The purpose of the study is to find out how a small dose of insulin might affect memory, the ability to concentrate, and improve your daily functioning in patients with schizophrenia and schizoaffective disorders. Insulin is not being used to treat diabetes in this study. The investigators propose a single dose, double-blinded, placebo-controlled trial of intranasal insulin in 40 subjects with schizophrenia or schizoaffective disorder to examine insulin's effect on cognition. The specific aims include: 1. Examine the effects of single doses of 40 IU intranasal insulin compared to placebo on cognitive functioning, including attention and memory. 2. Examine whether single dose of intranasal insulin administration will raise serum insulin level and decrease plasma glucose level Insulin will be delivered through an air spray pump into your nose. The investigators will be comparing one dose of insulin (40 International Units) with placebo, an inactive liquid.

Detailed description

Insulin signaling in the brain is associated with improved cognitive function in both animal and human studies. Intranasal administration of insulin, which is non-invasive and minimizes the risk of hypoglycemia, may represent a new intervention approach with the potential to improve cognition and real life functioning in this patient with schizophrenia.

Interventions

DRUGPlacebo

Placebo

DRUGInsulin (Humulin)

40 IU Intranasal Insulin will be administered once

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

* Age 18-65 years * Diagnosis of schizophrenia, any subtype or schizoaffective disorder, any subtype * Male or female * Stable dose of the current antipsychotic drug for at least one month * Well established compliance with out-patient treatment per treating clinician's judgement. * Able to complete the cognitive assessment battery (must be English speaking)

Exclusion criteria

* Inability to provide informed consent * Current substance abuse * On clozapine or olanzapine * Psychiatrically unstable per treating clinician's judgement. * Significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases etc. * Incapable to complete the cognitive battery assessment.

Design outcomes

Primary

Measure	Time frame	Description
Improvement in Cognitive Function- HVLT Immediate Recall Total (Number)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed the HVLT Immediate Recall Task. For this task, participants were read aloud a list of 12 words from three taxonomic categories. Participants were read the list three separate times, and after each reading were immediately asked to recall as many words from the list as they could. The number of words recalled successfully was measured before and after intranasal treatment. Values below represent posttreatment performance minus pretreatment performance.
Improvement in Cognitive Function- HVLT-Delayed Recall (Number)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed the HVLT word recall task after a 20-minute delay before and after intranasal treatment. In the HVLT delayed recall task, participants were asked to recall the same list of 12 words dictated in the immediate recall task 20 minutes after the completion of the immediate recall task. Words successfully recalled after the 20-minute delay were measured. Values below represent posttreatment performance minus pretreatment performance.
CPT d Score	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention (attention to a specific stimuli over a period of several minutes) before and after intranasal treatment. During this test, participants respond as quickly as possible to any consecutive presentation of identical stimuli on the computer screen. The stimuli (2, 3, and 4-digit targets) were presented with increasing cognitive load in successive blocks. Correct responses, responses made to the second of 2 identical stimuli presented in a row, were scored as hits. False alarms were also recorded. The d prime score is a score given to each participant on a scale of 0.0- 1.0 in which discrimination sensitivity is measured. A score of zero equates to no sensitivity, whereas a score of 1.0 equates to perfect sensitivity. Values below represent postreatment performance minus pretreatment performance.
Improvement in Cognitive Function- CPT Hits Rate (Proportion)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in the previous outcome measure (CPT d score). Hits rate refers to each participant's ability to correctly respond to two consecutive target presentations (i.e. correct responses). Hits rate was measured as a proportion of overall attempts (0= no hits, 1.0= 100% accuracy on hits). Values below represent posttreatment performance minus pretreatment performance.
Improvement in Cognitive Function- CPT Reaction Time of Hits (Milliseconds)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in detail in a previous outcome measure (CPT d score). Reaction time of hits refers to the average time each participant took to correctly respond to a stimuli in milliseconds. Values below represent posttreatment performance minus pretreatment performance.
Improvement in Cognitive Function- CPT False Alarm Rate (Proportion)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in detail in a previous outcome measure (CPT d score). False alarm rate refers to the proportion of overall attempts that were characterized as incorrect responses (responses to two non-identical targets). Values below represent posttreatment performance minus pretreatment performance.

Countries

United States

Participant flow

Recruitment details

Subjects were recruited from an urban community mental health clinic.

Pre-assignment details

Subjects who met DSM-IV criteria for schizophrenia or schizoaffective disorder were enrolled in the study (see inclusion/exclusion criteria). Subjects were randomly assigned to either the experimental group or placebo group.

Participants by arm

Arm	Count
Placebo (1) Subjects are given a one-time, single dose of placebo intranasal spray	15
Single-Dose Intranasal Insulin Subjects are given a one-time, single dose of intranasal insulin	15
Total	30

Baseline characteristics

Characteristic	Placebo (1)	Single-Dose Intranasal Insulin	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	15 Participants	15 Participants	30 Participants
Region of Enrollment United States	15 participants	15 participants	30 participants
Sex: Female, Male Female	10 Participants	10 Participants	20 Participants
Sex: Female, Male Male	5 Participants	5 Participants	10 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 15	0 / 15
serious Total, serious adverse events	0 / 15	0 / 15

Outcome results

Primary

CPT d Score

Subjects performed a computer-based test designed to measure sustained attention (attention to a specific stimuli over a period of several minutes) before and after intranasal treatment. During this test, participants respond as quickly as possible to any consecutive presentation of identical stimuli on the computer screen. The stimuli (2, 3, and 4-digit targets) were presented with increasing cognitive load in successive blocks. Correct responses, responses made to the second of 2 identical stimuli presented in a row, were scored as hits. False alarms were also recorded. The d prime score is a score given to each participant on a scale of 0.0- 1.0 in which discrimination sensitivity is measured. A score of zero equates to no sensitivity, whereas a score of 1.0 equates to perfect sensitivity. Values below represent postreatment performance minus pretreatment performance.