SNIFF 120: Study of Nasal Insulin to Fight Forgetfulness (120 Days) (SNIFF 120)

• ClinicalTrials.gov Identifier: NCT00438568
• Recruitment Status: Completed
• First Posted: February 22, 2007
• Last Update Posted: September 14, 2012
• Sponsor: University of Washington
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): University of Washington

Tracking Information

• First Submitted Date: February 21, 2007
• First Posted Date: February 22, 2007
• Last Update Posted Date: September 14, 2012
• Study Start Date: June 2006
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2007)

• Changes in cognition [ Time Frame: every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) ]
• glucose metabolism [ Time Frame: every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) ]
• plasma biological markers [ Time Frame: every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) ]

Original Primary Outcome Measures (submitted: February 21, 2007)

• Changes in cognition
• glucose metabolism
• plasma biological markers

Current Secondary Outcome Measures (submitted: December 20, 2007)

• CSF biological markers [ Time Frame: every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) ]
• cerebral glucose metabolism [ Time Frame: every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) ]

Original Secondary Outcome Measures (submitted: February 21, 2007)

• CSF biological markers
• cerebral glucose metabolism

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SNIFF 120: Study of Nasal Insulin to Fight Forgetfulness (120 Days)
• Official Title: Therapeutic Effects of Intranasal Insulin Administration in AD
• Brief Summary: The purpose of this study is to find out if insulin, when administered as a "nasal spray" into the nasal passages, improves memory in adults with mild cognitive impairment (MCI) or Alzheimer's disease.

Detailed Description

A growing body of evidence suggests that insulin plays a role in normal memory processes and that insulin abnormalities may contribute to cognitive and brain changes associated with Alzheimer's disease (AD). Interestingly, insulin administered to the nasal cavity is transported within a few minutes into the brain, but does not affect blood sugar or insulin levels.

This study will consist of a randomized double-blind, placebo-controlled parallel group trial in which 90 participants with AD or MCI receive daily intranasal administrations of either insulin (10 or 20 IU twice a day for a total dose of 20 or 40 IU per day) or placebo (saline twice a day) for 4 months. The study will examine the effects of intranasal insulin administration on cognition, cerebral glucose metabolism, and β-amyloid (Aβ) in cerebrospinal fluid (CSF) and plasma, testing the hypothesis that daily intranasal insulin administration for 4 months will facilitate memory for adults with AD, and adults with mild cognitive impairment (MCI). A subset of participants will have the option to participate in 2 sub-studies: PET scans (prior to and at the end of treatment) to determine whether intranasal insulin increases cerebral glucose metabolism; lumbar punctures (LPs) before and at the end of treatment to determine effects of intranasal insulin administration on CSF Aβ levels.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Mild Cognitive Impairment
• Alzheimer's Disease

Intervention

• Drug: Regular Insulin
  administered intra-nasally twice a day for 16 weeks
  Other Name: Novolin U-100
• Drug: Placebo
  administered intra-nasally twice a day for 16 weeks
  Other Name: saline

Study Arms

• Placebo Comparator: 1
  saline
  Intervention: Drug: Placebo
• Experimental: 2
  10 Units
  Intervention: Drug: Regular Insulin
• Experimental: 3
  20 Units
  Intervention: Drug: Regular Insulin

Publications *

• Reger MA, Watson GS, Frey WH 2nd, Baker LD, Cholerton B, Keeling ML, Belongia DA, Fishel MA, Plymate SR, Schellenberg GD, Cherrier MM, Craft S. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging. 2006 Mar;27(3):451-8. doi: 10.1016/j.neurobiolaging.2005.03.016. Epub 2005 Jun 16.
• Reger MA, Craft S. Intranasal insulin administration: a method for dissociating central and peripheral effects of insulin. Drugs Today (Barc). 2006 Nov;42(11):729-39. doi: 10.1358/dot.2006.42.11.1007675.
• Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, Cook DG, Peskind ER, Baker LD, Goldgaber D, Nie W, Asthana S, Plymate SR, Schwartz MW, Craft S. Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Arch Neurol. 2005 Oct;62(10):1539-44. doi: 10.1001/archneur.62.10.noc50112.
• Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. doi: 10.1001/archneurol.2011.233. Epub 2011 Sep 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 3, 2009): 173
• Original Enrollment (submitted: February 21, 2007): 90
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 55 or greater
• Good physical health
• Memory impairment with a diagnosis of mild cognitive impairment (MCI) or Alzheimer's disease (AD)
• Participants on stable doses of Memantine (Namenda) or cholinesterase inhibitors will be eligible

Exclusion Criteria:

• Chronic sinus problems/allergies with chronic use of nasal decongestants or antihistamines
• Significant neurologic disease that might affect cognition (other than AD), such as stroke, Parkinson's disease, multiple sclerosis, severe head injury with loss of consciousness for more than 30 minutes or with permanent neurologic symptoms
• Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease
• Preexisting diabetes or current or previous use of hypoglycemic agents or insulin; participants will be excluded if they have a fasting blood sugar greater than 165 on baseline OGTT
• Clinically significant elevations in liver function tests, cholesterol, or triglycerides
• Major psychiatric disorders (e.g., untreated major depression and schizophrenia)
• Chronic use of the following types of medications: anti-psychotic, anxiolytic, and opiates

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00438568
• Other Study ID Numbers: 30579-B; 5R01AG027415 ( U.S. NIH Grant/Contract ); 1R01AG027415-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Washington
• Original Responsible Party: Not Provided
• Current Study Sponsor: University of Washington
• Original Study Sponsor: National Institute on Aging (NIA)
• Collaborators: National Institute on Aging (NIA)

Investigators

• Principal Investigator: Suzanne Craft, PhD; University of Washington

• PRS Account: University of Washington
• Verification Date: September 2012