The Effect of Intranasal Insulin on Neurocognitive Function in Euthymic Patients With Bipolar Disorder
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      It is hypothesized that the intranasal administration of insulin will enhance
      hippocampal-dependent neurocognitive performance in euthymic patients with bipolar I or II
      disorder. This novel initiative represents a proof-of-concept study that insulin is salient
      to neurocognitive functioning and deficits in bipolar disorder and represents a novel and
      safe therapeutic avenue. The available literature suggests that the acute administration of
      intranasal insulin enhances cognition in memory impaired older adults with either Alzheimer's
      disease or minimal cognitive impairment. Prior research demonstrates a cognitive enhancing
      effect of insulin within one hour of the first intranasal insulin dose. Other studies suggest
      that the long-term administration of intranasal insulin (i.e. over eight weeks) in enhances
      memory performance in human volunteers. We aim to evaluate the acute and long-term effects of
      intranasal insulin administration in persons with bipolar disorder. As such we will be
      conducting the neuropsychological testing at three time points, the week before receiving
      insulin, within one hour of the first dose and after 8 weeks of insulin administration.
    

Detailed description: 
      Sixty verified euthymic individuals (age 18-60) with DSM-IV-TR defined Bipolar Disorder
      (diagnosis will be confirmed by the Mini International Neuropsychiatric Interview for the
      DSM-IV) will be enrolled. Individuals below the age of 18 and over 60 are excluded as they
      are not seen at the recruiting center. Enrollment into the study is voluntary. Eligible
      subjects will provide written informed consent. Subjects will be enrolled from the outpatient
      Mood Disorders Psychopharmacology Unit (MDPU), University health Network, University of
      Toronto. Study information and consent procedures will be provided by personnel other than
      the primary treatment provider.

      Euthymia (the absence of clinically meaningful symptoms) will be prospectively defined as a
      score of 3 or less with the Hamilton Rating Scale for Depression 7 item (HAMD-7) and a score
      of 7 or less on the Young Mania Rating Scale (YMRS) at initial assessment and at 1 month
      (baseline). The HAMD-7 and YMRS will be repeated at every follow-up visit.

      Conventional pharmacological treatments for bipolar disorder will be permitted (e.g. Lithium,
      anticonvulsant mood stabilizers, antipsychotics, antidepressants, anxiolytics/hypnotics,
      etc.). Medication regimens will remain stable throughout the duration of the study.
      Enrollment into the study is voluntary. Eligible subjects will provide written informed
      consent. Study information and consent procedures will be provided by personnel other than
      the primary treatment provider. Subjects will be enrolled from the outpatient Mood Disorders
      Psychopharmacology Unit, University Health Network, University of Toronto. Illness
      characteristics will be obtained from the patient interview and hospital medical records.

      Subjects will be compensated for sundry expenses (i.e. parking, public transport). Subjects
      will not receive financial compensation for being a participant in the study. The ongoing
      provision of care is not contingent on enrollment and/or completion of the study protocol.

      Subjects will be excluded if they are receiving corticosteroids or antihypertensive
      medications; another current Axis I psychiatric disorder; a neurological or medically
      unstable condition; substance or alcohol misuse in the past 3 months; or electroconvulsive
      therapy in the last year. Other exclusion criteria include the presence of diabetes mellitus
      or hyperglycemia, BMI equal or greater than 40 kg/m^2 or inability to provide written
      informed consent. Patients who are actively suicidal or evaluated as being a suicide risk
      will be excluded. Other reasons for discontinuation are voluntary discontinuation, failure to
      complete 1 month of euthymia, impaired fasting glucose (i.e. 6.1-6.9 mmol/L), non-compliance
      (i.e. failure to administer > 80% of the assigned treatment in any week). Insulin will be
      measured quantitatively on a weekly basis; subjects will also complete a diary of when they
      took intranasal insulin and their prescribed medication.

      The ongoing provision of care is not contingent on enrollment and/or completion of the study
      protocol. Furthermore, there will be ongoing communication with the subject's primary care
      provider in regards to their participation in this study.

      This is a randomized double-blind, placebo-controlled, parallel-group study.

      The initial visit entails the provision of detailed study information to a subject and
      obtainment of written informed consent from the subject. The subject will then meet a
      research team member at a later date for a screening visit. This study requires a total of 12
      visits.

      Neuropsychological testing will be conducted at 3 time points:

        1. Baseline (Visit 3)

        2. Within 60 minutes of the first administration of randomized treatment (Visit 4)

        3. Endpoint (Visit 12)
    

Intervention name(s): Intranasal Insulin; Diluent
Intervention type(s): Drug; Drug
Intervention description(s): Intranasal spray; 40 IU qid; 8 weeks; Intranasal spray; 8 weeks
Intervention MeSH terms: Insulin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Bipolar Disorder, memory, executive functioning