Trial Outcomes & Findings for Intranasal Insulin Treatment in Patients With Schizophrenia (NCT NCT00575666)

NCT ID: NCT00575666

Last Updated: 2012-12-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 45 participants
• Primary outcome timeframe: Week 8
• Results posted on: 2012-12-17

Participant Flow

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.

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.

Participant milestones

Measure	Intervention: Insulin Intranasal insulin treatment, daily dosage 160 IU insulin for 8 weeks with a 4 week follow-up	Intervention: Placebo Placebo group, daily dosage 160 IU placebo for 8 weeks with 4 week follow-up
Overall Study STARTED	21	24
Overall Study COMPLETED	17	21
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Measure	Intervention: Insulin Intranasal insulin treatment, daily dosage 160 IU insulin for 8 weeks with a 4 week follow-up	Intervention: Placebo Placebo group, daily dosage 160 IU placebo for 8 weeks with 4 week follow-up
Overall Study Withdrawal by Subject	3	2
Overall Study Physician Decision	1	1

Baseline Characteristics

Intranasal Insulin Treatment in Patients With Schizophrenia

Baseline characteristics by cohort

Measure	Intervention: Insulin n=21 Participants Intranasal insulin treatment, daily dosage 160 IU insulin for 8 weeks with a 4 week follow-up	Intervention: Placebo n=24 Participants Placebo group, daily dosage 160 IU placebo for 8 weeks with 4 week follow-up	Total n=45 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	21 Participants n=5 Participants	24 Participants n=7 Participants	45 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	49.2 years STANDARD_DEVIATION 9.3 • n=5 Participants	43.8 years STANDARD_DEVIATION 9.2 • n=7 Participants	46.0 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	24 participants n=7 Participants	45 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- Digit Span Total	13.3 Items correct Standard Deviation 4.0	14.1 Items correct Standard Deviation 4.9

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- Verbal Fluency	27.9 Words correct Standard Deviation 11.6	28.0 Words correct Standard Deviation 13.3

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- HVLT Immediate Recall Total	21.4 Words correct Standard Deviation 8.4	23.6 Words correct Standard Deviation 7.1

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- HVLT Delayed Recall Total	6.8 Words correct Standard Deviation 3.6	7.8 Words correct Standard Deviation 3.2

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- Trails A	60.6 Seconds Standard Deviation 35	52.3 Seconds Standard Deviation 23.2

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- Trails B	131.5 Seconds Standard Deviation 62	118.6 Seconds Standard Deviation 44.1

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- CPT D Prime Score	1.9 D prime score Standard Deviation 1	2.1 D prime score Standard Deviation 1

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- CPT Hits Rate (Proportion)	0.7 Proportion of total hits Standard Deviation 0.2	0.7 Proportion of total hits Standard Deviation 0.2

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- CPT Reaction Time of Hits (Milliseconds)	554.1 Milliseconds Standard Deviation 109.4	552.9 Milliseconds Standard Deviation 73.7

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on cognitive function measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Cognitive Function- CPT False-alarm Rate (Proportion)	0.1 Proportion of total hits Standard Deviation 0.1	0.1 Proportion of total hits Standard Deviation 0.1

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on psychopathology measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Psychopathology- PANSS Total	74.3 units on a scale Standard Deviation 19.5	74.1 units on a scale Standard Deviation 13.5

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on psychopathology measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Psychopathology- PANSS Positive	17.2 units on a scale Standard Deviation 5.6	16.8 units on a scale Standard Deviation 5.1

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on psychopathology measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Psychopathology- PANSS Negative	20.8 units on a scale Standard Deviation 6.0	20.7 units on a scale Standard Deviation 5.8

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on psychopathology measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Psychopathology- PANSS General Psychopathology	36.3 units on a scale Standard Deviation 9.9	36.6 units on a scale Standard Deviation 7.4

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on psychopathology measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Psychopathology- SANS Total	30.8 units on a scale Standard Deviation 15.2	33.5 units on a scale Standard Deviation 14.3

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on psychopathology measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Psychopathology- CDSS Total	2.1 units on a scale Standard Deviation 3.2	2.7 units on a scale Standard Deviation 4.4

PRIMARY outcome

Timeframe: Week 8

Population: All subjects who completed the study for each Arm/Group were analyzed on psychopathology measures; study completion allows for calculation of change scores.

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.

Outcome measures

Measure	Humulin n=17 Participants 160 IU per day for 8 weeks	Placebo n=21 Participants 160 IU per day for 8 weeks
Psychopathology- QLS Total	70.9 units on a scale Standard Deviation 16.3	67 units on a scale Standard Deviation 16.8

Adverse Events

Intervention: Insulin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intervention: Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Xiaoduo Fan, MD, MPH, MS

UMass Medical School

Phone: 508-856-3881

Email: Xiaoduo.Fan@umassmed.edu

Results disclosure agreements

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