Intranasal Insulin Treatment in Patients With Schizophrenia

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00575666

Enrollment

Registered

2007-12-18

Start date

2007-12-31

Completion date

2010-09-30

Last updated

2012-12-17

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

Conditions

Schizophrenia

Keywords

cognition, psychopathology

Brief summary

This study is an 8-week, randomized, double-blind, placebo-controlled trial of intranasal insulin as an adjunctive therapy, with a 4-week follow-up, in 60 non-diabetic schizophrenia subjects to examine insulin's effect on psychopathology and cognition. In addition, the study will examine insulin's effects on weight, food intake, resting energy expenditure, and body composition.

Detailed description

The specific aims include: Primary aims 1. Examine the efficacy of intranasal regular insulin (40 IU 4 times per day) in improving cognitive deficits in patients with schizophrenia. 2. Examine the efficacy of intranasal regular insulin in improving negative symptoms and positive symptoms of schizophrenia. Secondary aims 1. Examine intranasal insulin's effects on weight, food intake and resting energy expenditure. 2. Examine intranasal insulin's effects on body composition, waist circumference, and waist/hip ratio.

Interventions

DRUGInsulin or Placebo

intranasal, 40IU, 4 times daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

1. Age 18-65 years. 2. Diagnosis of schizophrenia, any subtype or schizoaffective disorder, any subtype. 3. Stable dose of the current antipsychotic drug for at least one month. 4. Well established compliance with outpatient treatment per treating clinician's judgement. 5. Able to complete the cognitive assessment battery (must be English speaking). 6. Female subjects will be eligible to participate in the study if they are of non-childbearing potential or of child-bearing potential and willing to practice appropriate birth control methods (complete abstinence from sexual intercourse, female sterilization, sterilization of male partner, implants of levonorgestrel, injectable progestogen, oral contraceptives, intrauterine devices, or double barrier methods of contraception using spermicide with either a condom or diaphragm) during the study.

Exclusion criteria

1. Inability to provide informed consent. 2. Current substance abuse. 3. Psychiatrically unstable per treating clinician's judgement. 4. Significant medical illnesses including uncontrolled hypertension, diabetes, seizure. disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases. 5. Pregnancy or breastfeeding.

Design outcomes

Primary

Measure	Time frame	Description
Cognitive Function- Digit Span Total	Week 8	Subjects completed the digit span task. Assessment was completed at Screening/Baseline, Week 4, and Week 8. Higher scores represent higher recall accuracy, and therefore less advanced psychopathology. Min score= 0, Max score= 30. Week 8 values are displayed below.
Cognitive Function- Verbal Fluency	Week 8	Subjects completed a verbal fluency test. Assessment was completed at Screening/Baseline, Week 4, and Week 8. Higher scores represent higher levels of verbal fluency, and therefore less advanced psychopathology. Min score= 0, Max score= N/A. Week 8 values are displayed below.
Cognitive Function- HVLT Immediate Recall Total	Week 8	Subjects completed a word recall task. Assessment was completed at Screening/Baseline, Week 4, and Week 8. Higher scores represent higher recall accuracy, and therefore less advanced psychopathology. Min score= 0, Max score= 36. Week 8 values are displayed below.
Cognitive Function- HVLT Delayed Recall Total	Week 8	Subjects completed a delayed word recall task. Assessments were completed at Screening/Baseline, Week 4, and Week 8. Higher scores represent higher recall accuracy, and therefore less advanced psychopathology. Min score= 0, Max score= 12. Week 8 values are displayed below.
Cognitive Function- Trails A	Week 8	Subjects completed a timed trails (i.e. connect-the-dots) test. Assessments were completed at Screening/Baseline, Week 4, and Week 8. Scores were measured by time to complete in seconds. Max score= N/A. Lower values represent less advanced psychopathology. Week 8 values are displayed below.
Cognitive Function- Trails B	Week 8	Subjects completed a timed trails (i.e. connect the dots) test. Assessments were completed at Screening/Baseline, Week 4, and Week 8. Scores were mesured by time to complete in seconds. Max score= N/A. Lower values represent less advanced psychopathology. Week 8 values are displayed below.
Cognitive Function- CPT D Prime Score	Week 8	Subjects completed a computer-based cognitive test designed to measure sustained attention (attention to a specific stimulus 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. Higher scores represent less advanced psychopathology. Week 8 values are displayed below.
Cognitive Function- CPT Hits Rate (Proportion)	Week 8	Subjects completed a computer-based cognitive test. The test is described in detail in a previous outcome measure (CPT d prime score). Hits rate was defined as the proportion of correct responses to the relevant stimuli (response to two identical targets) compared to total responses (total hits). Assessments were completed at Screening/Baseline, Week 4, and Week 8. Hits rate as a proportion of total hits was measured. Min score= 0, Max score= 1.0. Higher values represent higher stimulus recognition accuracy, and thus less advanced psychopathology. Week 8 values are displayed below.
Cognitive Function- CPT Reaction Time of Hits (Milliseconds)	Week 8	Subjects completed a computer-based cognitive functioning test designed to measure sustained attention (attention to a stimulus over a period of several minutes). The test is described in detail in a previous outcome measure (CPT d prime score). Reaction time of hits is defined as the average time each participant took to respond correctly to relevant stimuli. Assessments were completed at Screening/Baseline, Week 4, and Week 8. Reaction time was measured in milliseconds. Max score= N/A. Lower values represent less advanced psychopathology. Week 8 values are displayed below.
Cognitive Function- CPT False-alarm Rate (Proportion)	Week 8	Subjects completed a computer-based cognitive functioning test designed to measure sustained attention (attention to a stimulus over a period of several minutes). False alarm rate is defined as the proportion of overall hits that were in response to an incorrect stimulus (two consecutive non-identical targets). Assessments were completed at Screening/Baseline, Week 4, and Week 8. False-alarm hits were measured as a proportion of total hits. Min score= 0, Max score= 1.0. Lower values represent higher hit accuracy and less advanced psychopathology. Week 8 values are displayed below.
Psychopathology- PANSS Total	Week 8	Positive symptoms, negative symptoms, and general psychopatholgy of schizophrenia were measured at Screening/Baseline, Week 4, and Week 8. The assessment consisted of 30 total items, with each item measured on a seven-point scale (1= absent, 4= moderate, 7= extreme). Min score= 30, Max score= 210. Higher scores represent more advanced psychopathology. Week 8 values are displayed below.
Psychopathology- PANSS Positive	Week 8	Positive symptoms of schizophrenia were measured at Screening/Baseline, Week 4, and Week 8. The assessment consisted of seven items, with each item measured on a seven-point scale (1= absent, 4= moderate, 7= extreme). Min score= 7, Max score= 49. Higher scores represent more advanced psychopathology. Week 8 values are displayed below.
Psychopathology- PANSS Negative	Week 8	Negative symptoms of schizophrenia were measured at Screening/Baseline, Week 4, and Week 8. Assessment consisted of seven-items, with each item measured on a seven-point scale (1= absent, 4= moderate, 7= extreme). Min score= 7, Max score= 49. Higher scores represent more advanced psychopathology. Week 8 values are displayed below.
Psychopathology- PANSS General Psychopathology	Week 8	General psychopathology was measured at Screening/Baseline, Week 4, and Week 8. The assessment consisted of 16 items, with each item measured on a seven-point scale (1= absent, 4= moderate, 7= extreme). Min score= 16, Max score= 112. Higher scores represent more advanced psychopathology. Week 8 values are displayed below.
Psychopathology- SANS Total	Week 8	Negative symptoms of schizophrenia were measured at Screening/Baseline, Week 4, and Week 8. Assessment consisted of 25 items, with each item measured on a six-point scale (0= none, 3= moderate, 5= severe). Min score= 0, Max score= 125. Higher scores represent more advanced psychopathology. Week 8 values are displayed below.
Psychopathology- CDSS Total	Week 8	Symptoms of depression were measured at Screening/Baseline, Week 4, and Week 8. Assessment consisted of 9 items, with each item measured on a four-point scale (0= absent, 3= severe). Min score= 0, Max score= 27. Higher scores represent more advanced psychopathology. Week 8 values are displayed below.
Psychopathology- QLS Total	Week 8	Quality of life was measured at Screening/Baseline, Week 4, and Week 8. Assessment consisted of 21 items, with each item measured on a seven-point scale (0= not present, 3= sometimes present, 6= always present). Min score= 0, Max score= 126. Higher scores represent lower quality of life. Week 8 values are displayed below.

Countries

United States

Participant flow

Recruitment details

Subjects were recruited from the Freedom Trail Clinic at the Erich Lindemann Mental Health Center and were studied at the Massachusetts General Hospital Clinical Research Center (MGH CRC), Boston.

Pre-assignment details

After providing written informed consent, subjects underwent a diagnostic evaluation by a research psychiatrist using the Structured Clinical Interview for DSM-IV (SCID). All subjects were screened and enrolled based on eligibility criteria. Baseline study assessments were completed prior to intervention.

Participants by arm

Arm	Count
Intervention: Insulin Intranasal insulin treatment, daily dosage 160 IU insulin for 8 weeks with a 4 week follow-up	21
Intervention: Placebo Placebo group, daily dosage 160 IU placebo for 8 weeks with 4 week follow-up	24
Total	45

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Physician Decision	1	1
Overall Study	Withdrawal by Subject	3	2

Baseline characteristics

Characteristic	Total	Intervention: Insulin	Intervention: Placebo
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	45 Participants	21 Participants	24 Participants
Age Continuous	46.0 years STANDARD_DEVIATION 9	49.2 years STANDARD_DEVIATION 9.3	43.8 years STANDARD_DEVIATION 9.2
Region of Enrollment United States	45 participants	21 participants	24 participants
Sex: Female, Male Female	9 Participants	3 Participants	6 Participants
Sex: Female, Male Male	36 Participants	18 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 21	0 / 24
serious Total, serious adverse events	0 / 21	0 / 24

Outcome results

Primary

Cognitive Function- CPT D Prime Score

Subjects completed a computer-based cognitive test designed to measure sustained attention (attention to a specific stimulus 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. Higher scores represent less advanced psychopathology. Week 8 values are displayed below.

Time frame: Week 8