Amnestic Mild Cognitive ImpairmentPhase 2/3NCT01767909
The Study of Nasal Insulin in the Fight Against Forgetfulness (SNIFF)
A Phase 2/3 study testing Insulin (Humulin® R U-100) in people with Amnestic Mild Cognitive Impairment and Alzheimer's Disease, run by University of Southern California at 25 sites in United States.
Trial summary
An urgent need exists to find effective treatments for Alzheimer's disease (AD) that can arrest or reverse the disease at its earliest stages. The emotional and financial burden of AD to patients, family members, and society is enormous, and is predicted to grow exponentially as the median population age increases. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Amnestic Mild Cognitive Impairment, Alzheimer's Disease
- What is being tested?
- Insulin (Humulin® R U-100)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 25 sitesUnited States
- Study dates
- 8 Jan 2014to 11 Dec 2018
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fluent in English or Spanish
- Diagnosis of aMCI by Petersen criteria or probable AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
- Mini Mental State Examination (MMSE) score at screening is greater than or equal to 20
- Clinical Dementia Rating is 0.5-1 at screening
- Logical Memory is less than or equal to 8 for 16 or more years of education, less than or equal to 4 for 8-15 years of education, less than or equal to 2 for 0-7 years of education. Scores measured at screening on Delayed Paragraph Recall (Paragraph A only) from the Wechsler Memory Scale-Revised
- Able to complete baseline assessments
Show all 15Show fewer
- Modified Hachinski score of less than or equal to 4
- A study partner able to accompany the participant to most visits and answer questions about the participant
- The study partner must have direct contact with the participant more than 2 days per week (minimum of 10 hours per week) and provide supervision of drug administration as needed
- Stable medical condition for 3 months prior to screening visit
- Stable medications for 4 weeks prior to the screening and baseline visits
- Stable use of permitted medications
- At least six years of education or work history
- Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
- Visual and auditory acuity adequate for neuropsychological testing
Who cannot join
- A diagnosis of dementia other than probable AD
- Probable AD with Down syndrome
- History of clinically significant stroke
- Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- Sensory impairment that would preclude the participant from participating in or cooperating with the protocol
- Diabetes (type 1 or type II) requiring pharmacologic treatment (including both insulin dependent and non-insulin dependent diabetes mellitus)
Show all 17Show fewer
- Current or past use of insulin or any other anti-diabetic medication
- Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, endocrine, metabolic, renal or other systemic disease or laboratory abnormality.
- Active neoplastic disease, history of cancer five years prior to screening (history of skin melanoma or stable prostate cancer are not excluded)
- History of seizure within the past five years
- Pregnancy or possible pregnancy
- Contraindications to Lumbar Puncture (LP) procedure: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets is less than 100,000 or history of bleeding disorder
- Use of anticoagulants warfarin (Coumadin) and dabigatran (Pradaxa) due to LP requirement
- Contraindications for MRI (claustrophobia, craniofacial metal implants of any kind, pacemakers)
- Residence in a skilled nursing facility at screening
- Use of an investigational agent within two months or screening visit
- Regular use of narcotics, anticonvulsants, medications with significant anticholinergic activity, antiparkinsonian medications or any other exclusionary medications
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21224
Case Western Reserve University
Beachwood, Ohio, 44122
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Roper St. Francis Hospital
Charleston, South Carolina, 29401
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60614
Baylor College of Medicine
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of California, Irvine
Irvine, California, 92697
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224
University of Kentucky
Lexington, Kentucky, 40504
Yale University School of Medicine
New Haven, Connecticut, 06510
Mount Sinai School of Medicine
New York, New York, 10029
Banner Alzheimer's Institute
Phoenix, Arizona, 85006
Barrow Neurology Clinics
Phoenix, Arizona, 85013
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
University of Rochester Medical Center
Rochester, New York, 14620
U of WA / VA Puget Sound Alzheimer's Disease Research Center
Seattle, Washington, 98108
Tulsa Clinical Research
Tulsa, Oklahoma, 74104
Georgetown University
Washington D.C., District of Columbia, 20057
Howard University
Washington D.C., District of Columbia, 20060
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Therapeutic Effects of Intranasally-Administered Insulin in Adults With Amnestic Mild Cognitive Impairment (aMCI) or Mild Alzheimer's Disease (AD)
An urgent need exists to find effective treatments for Alzheimer's disease (AD) that can arrest or reverse the disease at its earliest stages. The emotional and financial burden of AD to patients, family members, and society is enormous, and is predicted to grow exponentially as the median population age increases. Current FDA-approved therapies are modestly effective at best. This study will examine a novel therapeutic approach using intranasal insulin (INI) that has shown promise in short-term clinical trials. If successful, information gained from the study has the potential to move INI forward rapidly as a therapy for AD. The study will also provide evidence for the mechanisms through which INI may produce benefits by examining key cerebral spinal fluid (CSF) biomarkers and hippocampal/entorhinal atrophy. These results will have considerable clinical and scientific significance, and provide therapeutically-relevant knowledge about insulin's effects on AD pathophysiology. Growing evidence has shown that insulin carries out multiple functions in the brain, and that insulin dysregulation may contribute to AD pathogenesis.
This study will examine the effects of intranasally-administered insulin on cognition, entorhinal cortex and hippocampal atrophy, and cerebrospinal fluid (CSF) biomarkers in amnestic mild cognitive impairment (aMCI) or mild AD. It is hypothesized that after 12 months of treatment with INI compared to placebo, subjects will improve performance on a global measure of cognition, on a memory composite and on daily function. In addition to the examination of CSF biomarkers and hippocampal and entorhinal atrophy, the study aims to examine whether baseline AD biomarker profile, gender, or Apolipoprotein epsilon 4 (APOE-ε4) allele carriage predict treatment response.
In this study, 240 people with aMCI or AD will be given either INI or placebo for 12 months, following an open-label period of 6 months where all participants will be given active drug. The study uses insulin as a therapeutic agent and intranasal administration focusing on nose to brain transport as a mode of delivery.
- Being tested
- Insulin (Humulin® R U-100), Placebo
- Keywords
- Intranasal insulin, Alzheimer's disease, Amnestic mild cognitive impairment, Dementia, Brain diseases, Memory problems, Mental disorders, Cognitive disorders
- Medical subject headings
- Alzheimer Disease, Dementia, Brain Diseases, Memory Disorders, Mental Disorders, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin (Humulin® R U-100)Drug
20 IU bid taken twice daily (approximately 30 minutes after breakfast and dinner) for a total of 40 IU daily, which will be administered intranasally. The device used to administer insulin releases a metered dose into a chamber covering the participant's nose. The insulin is then inhaled by breathing evenly over a specified period.
PlaceboDrug
Placebo taken twice daily (approximately 30 minutes after breakfast and dinner), which will be administered intranasally. The device used to administer placebo releases a metered dose into a chamber covering the participant's nose. The placebo is then inhaled by breathing evenly over a specified period.
| Study group | Role | What they receive |
|---|---|---|
| Insulin (Humulin® R U-100) | Experimental | 120 subjects will take two daily doses of INI (20 IU bid for a total daily dose of 40 IU) approximately 30 minutes after breakfast and dinner for 12 months. A 6-month open label period will follow in which all participants will receive INI. Receives: Drug: Insulin (Humulin® R U-100) |
| Placebo | Placebo comparator | 120 subjects will take two daily doses of placebo approximately 30 minutes after breakfast and dinner for 12 months. A 6-month open label period will follow in which all participants will receive INI. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Global Measure of Cognition as Measured by the Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog12)
The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. The ADAS-Cog12 version was used in this study which includes Delayed Word Recall - a measure of episodic memory. Scores from the original portion of the test range from 0 (best) to 70 (worse) and then number of items not recalled ranging from 0-10 is added for a maximum score of 80. A positive change indicates cognitive worsening.
Measured: 12 months (blinded phase) followed by 6 months (open label phase)
Secondary outcomes (5)
Change in Memory Composite as Measured by Story Recall (Immediate Paragraph Recall and Delayed Paragraph Recall) and Free and Cued Selective Reminding Test (FCSRT)
Memory Composite is composed from Story Recall (both Immediate Paragraph Recall and Delayed Paragraph Recall) and the Free and Cued Selective Reminding Test (FCSRT). Each of the three component scores were normalized by subtracting the baseline sample mean, and dividing by the baseline sample standard deviation, to form three separately standardized z-scores with mean 0 and standard deviation 1. The three Z-scores were summed to form the memory composite. No other standardization was performed on the sum. If any of Immediate Paragraph Recall, Delayed Paragraph Recall and FCSRT is missing, the memory composite is missing. Higher scores indicate better performance. In this study the scores ranged from about -4.74 to 9.15 at baseline, and about -5.10 to 9.43 across all visits over 12 months.
Measured: 12 months (blinded phase) followed by 6 months (open label phase)
Change in Daily Functioning as Measured by the ADCS-MCI Activities of Daily Living (ADCS-ADL-MCI)
The Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS-ADL) is an activities of daily living questionnaire aimed at detecting functional decline in people with Mild Cognitive Impairment (MCI). In a structured interview format, informants are queried as to whether participants attempted each item in the inventory during the prior 4 weeks and their level of performance. The questions focus predominantly on instrumental activities of daily living scales (e.g. shopping, preparing meals, using household appliances, keeping appointments, reading). The total score can range from 0-54. A higher score indicates greater functional ability.
Measured: 12 months (blinded phase) and 6 months (open label phase)
Change in Cognitive Deficit as Measured by Clinical Dementia Rating - Sum of Boxes (CDR-SB)
The Clinical Dementia Rating - Sum of Boxes (CDR-SB) is administered as a structured interview with the participant and study partner, where impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", are added together to give the CDR-Sum of Boxes which ranges from 0-18 with higher scores indicated more impairment.
Measured: 12 months (blinded phase) followed by 6 months (open label phase)
Change in Hippocampal and Entorhinal Atrophy as Measured by Magnetic Resonance Imaging (MRI)
MRI will be used to assess the effect of treatment on rate of hippocampal and entorhinal atrophy, and conduct exploratory analyses of other brain regions. Volume change was normalized to the participant's own intracranial volume to account for each participant's brain size.
Measured: Screen and Month 12
Change in CSF Biomarkers of AD
Quantify Abeta and Tau biomarkers in CSF
Measured: Baseline and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2013 (estimated)
- Study start8 Jan 2014
- Primary completion11 Dec 2018
- Study completion11 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Amnestic Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), Alzheimer's Therapeutic Research Institute, Wake Forest University Health Sciences
- Responsible party
- Principal investigator, Paul S. Aisen, University of Southern California
- Investigators
- Suzanne Craft, PhD, Study director, Wake Forest University Health SciencesPaul Aisen, MD, Study director, USC Alzheimer's Therapeutic Research Institute (ATRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01767909
- Sponsor's protocol ID
- ADC-046-INI
- Other IDs
- RF1AG041845
- Status last verified
- Nov 2024
- First submitted
- 10 Jan 2013
- Last updated
- 20 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21911655Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology. 1998 Jan;50(1):164-8. doi: 10.1212/wnl.50.1.164.
PubMed 9443474Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology. 2008 Feb 5;70(6):440-8. doi: 10.1212/01.WNL.0000265401.62434.36. Epub 2007 Oct 17.
PubMed 17942819Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S. Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol. 2011 Jan;68(1):51-7. doi: 10.1001/archneurol.2010.225. Epub 2010 Sep 13.
PubMed 20837822Jimenez-Maggiora GA, Donohue MC, Rafii MS, Raman R, Aisen PS. Artificial intelligence-enabled safety monitoring in Alzheimer's disease clinical trials. J Prev Alzheimers Dis. 2025 Jan;12(1):100002. doi: 10.1016/j.tjpad.2024.100002. Epub 2025 Jan 1.
PubMed 39800465Donohue MC, Langford O, Insel PS, van Dyck CH, Petersen RC, Craft S, Sethuraman G, Raman R, Aisen PS; Alzheimer's Disease Neuroimaging Initiative. Natural cubic splines for the analysis of Alzheimer's clinical trials. Pharm Stat. 2023 May-Jun;22(3):508-519. doi: 10.1002/pst.2285. Epub 2023 Jan 10.
PubMed 36627206Kellar D, Lockhart SN, Aisen P, Raman R, Rissman RA, Brewer J, Craft S. Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer's Disease. J Prev Alzheimers Dis. 2021;8(3):240-248. doi: 10.14283/jpad.2021.14.
PubMed 34101779Craft S, Raman R, Chow TW, Rafii MS, Sun CK, Rissman RA, Donohue MC, Brewer JB, Jenkins C, Harless K, Gessert D, Aisen PS. Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2020 Sep 1;77(9):1099-1109. doi: 10.1001/jamaneurol.2020.1840.
PubMed 32568367
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Effects of Intranasally-Administered Insulin in Adults With Amnestic Mild Cognitive Impairment (aMCI) or Mild Alzheimer's Disease (AD)
- ClinicalTrials.gov ID
- NCT01767909
- Acronym / sponsor ID
- ADC-046-INI
- Keywords
- Intranasal insulin, Alzheimer's disease, Amnestic mild cognitive impairment, Dementia, Brain diseases, Memory problems, Mental disorders, Cognitive disorders
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), Alzheimer's Therapeutic Research Institute, Wake Forest University Health Sciences
- Study start
- 8 Jan 2014 (actual)
- Primary completion
- 11 Dec 2018 (actual)
- Study completion
- 11 Dec 2018 (actual)
- First posted
- 15 Jan 2013 (estimated)
- Results
- Posted 18 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An urgent need exists to find effective treatments for Alzheimer's disease (AD) that can arrest or reverse the disease at its earliest stages. The emotional and financial burden of AD to patients, family members, and society is enormous, and is predicted to grow exponentially as the median population age increases. Current FDA-approved therapies are modestly effective at best. This study will examine a novel therapeutic approach using intranasal insulin (INI) that has shown promise in short-term clinical trials. If successful, information gained from the study has the potential to move INI forward rapidly as a therapy for AD. The study will also provide evidence for the mechanisms through which INI may produce benefits by examining key cerebral spinal fluid (CSF) biomarkers and hippocampal/entorhinal atrophy. These results will have considerable clinical and scientific significance, and provide therapeutically-relevant knowledge about insulin's effects on AD pathophysiology. Growing evidence has shown that insulin carries out multiple functions in the brain, and that insulin dysregulation may contribute to AD pathogenesis.
This study will examine the effects of intranasally-administered insulin on cognition, entorhinal cortex and hippocampal atrophy, and cerebrospinal fluid (CSF) biomarkers in amnestic mild cognitive impairment (aMCI) or mild AD. It is hypothesized that after 12 months of treatment with INI compared to placebo, subjects will improve performance on a global measure of cognition, on a memory composite and on daily function. In addition to the examination of CSF biomarkers and hippocampal and entorhinal atrophy, the study aims to examine whether baseline AD biomarker profile, gender, or Apolipoprotein epsilon 4 (APOE-ε4) allele carriage predict treatment response.
In this study, 240 people with aMCI or AD will be given either INI or placebo for 12 months, following an open-label period of 6 months where all participants will be given active drug. The study uses insulin as a therapeutic agent and intranasal administration focusing on nose to brain transport as a mode of delivery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin (Humulin® R U-100) | Experimental | Drug: Insulin (Humulin® R U-100)120 subjects will take two daily doses of INI (20 IU bid for a total daily dose of 40 IU) approximately 30 minutes after breakfast and dinner for 12 months. A 6-month open label period will follow in which all participants will receive INI. |
| Placebo | Placebo comparator | Drug: Placebo120 subjects will take two daily doses of placebo approximately 30 minutes after breakfast and dinner for 12 months. A 6-month open label period will follow in which all participants will receive INI. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Fluent in English or Spanish
- Diagnosis of aMCI by Petersen criteria or probable AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
- Mini Mental State Examination (MMSE) score at screening is greater than or equal to 20
- Clinical Dementia Rating is 0.5-1 at screening
- Logical Memory is less than or equal to 8 for 16 or more years of education, less than or equal to 4 for 8-15 years of education, less than or equal to 2 for 0-7 years of education. Scores measured at screening on Delayed Paragraph Recall (Paragraph A only) from the Wechsler Memory Scale-Revised
Key exclusion criteria (17 listed)
- A diagnosis of dementia other than probable AD
- Probable AD with Down syndrome
- History of clinically significant stroke
- Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- Sensory impairment that would preclude the participant from participating in or cooperating with the protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin (Humulin® R U-100)20 IU bid taken twice daily (approximately 30 minutes after breakfast and dinner) for a total of 40 IU daily, which will be administered intranasally. The device used to administer insulin releases a metered dose into a chamber covering the participant's nose. The insulin is then inhaled by breathing evenly over a specified period. | Drug | Insulin (Humulin® R U-100) |
| PlaceboPlacebo taken twice daily (approximately 30 minutes after breakfast and dinner), which will be administered intranasally. The device used to administer placebo releases a metered dose into a chamber covering the participant's nose. The placebo is then inhaled by breathing evenly over a specified period. | Drug | Placebo |
Primary outcome
Change in Global Measure of Cognition as Measured by the Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog12)
Time frame: 12 months (blinded phase) followed by 6 months (open label phase)
The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. The ADAS-Cog12 version was used in this study which includes Delayed Word Recall - a measure of episodic memory. Scores from the original portion of the test range from 0 (best) to 70 (worse) and then number of items not recalled ranging from 0-10 is added for a maximum score of 80. A positive change indicates cognitive worsening.
5 secondary outcomes
Change in Memory Composite as Measured by Story Recall (Immediate Paragraph Recall and Delayed Paragraph Recall) and Free and Cued Selective Reminding Test (FCSRT)
Time frame: 12 months (blinded phase) followed by 6 months (open label phase)
Change in Daily Functioning as Measured by the ADCS-MCI Activities of Daily Living (ADCS-ADL-MCI)
Time frame: 12 months (blinded phase) and 6 months (open label phase)
Change in Cognitive Deficit as Measured by Clinical Dementia Rating - Sum of Boxes (CDR-SB)
Time frame: 12 months (blinded phase) followed by 6 months (open label phase)
Change in Hippocampal and Entorhinal Atrophy as Measured by Magnetic Resonance Imaging (MRI)
Time frame: Screen and Month 12
Change in CSF Biomarkers of AD
Time frame: Baseline and Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21911655Craft 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.
- Background: PubMed 9443474Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology. 1998 Jan;50(1):164-8. doi: 10.1212/wnl.50.1.164.
- Background: PubMed 17942819Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology. 2008 Feb 5;70(6):440-8. doi: 10.1212/01.WNL.0000265401.62434.36. Epub 2007 Oct 17.
- Background: PubMed 20837822Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S. Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol. 2011 Jan;68(1):51-7. doi: 10.1001/archneurol.2010.225. Epub 2010 Sep 13.
- Derived from this study: PubMed 39800465Jimenez-Maggiora GA, Donohue MC, Rafii MS, Raman R, Aisen PS. Artificial intelligence-enabled safety monitoring in Alzheimer's disease clinical trials. J Prev Alzheimers Dis. 2025 Jan;12(1):100002. doi: 10.1016/j.tjpad.2024.100002. Epub 2025 Jan 1.
- Derived from this study: PubMed 36627206Donohue MC, Langford O, Insel PS, van Dyck CH, Petersen RC, Craft S, Sethuraman G, Raman R, Aisen PS; Alzheimer's Disease Neuroimaging Initiative. Natural cubic splines for the analysis of Alzheimer's clinical trials. Pharm Stat. 2023 May-Jun;22(3):508-519. doi: 10.1002/pst.2285. Epub 2023 Jan 10.
- Derived from this study: PubMed 34101779Kellar D, Lockhart SN, Aisen P, Raman R, Rissman RA, Brewer J, Craft S. Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer's Disease. J Prev Alzheimers Dis. 2021;8(3):240-248. doi: 10.14283/jpad.2021.14.
- Derived from this study: PubMed 32568367Craft S, Raman R, Chow TW, Rafii MS, Sun CK, Rissman RA, Donohue MC, Brewer JB, Jenkins C, Harless K, Gessert D, Aisen PS. Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2020 Sep 1;77(9):1099-1109. doi: 10.1001/jamaneurol.2020.1840.
- Alzheimer's Therapeutic Research Institute (ATRI)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suzanne Craft, PhD study director
Wake Forest University Health Sciences
Paul Aisen, MD study director
USC Alzheimer's Therapeutic Research Institute (ATRI)
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Insulin (Humulin® R U-100) in people with Amnestic Mild Cognitive Impairment and Alzheimer's Disease, run by University of Southern California at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Global Measure of Cognition as Measured by the Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog12) (time frame: 12 months (blinded phase) followed by 6 months (open label phase)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01767909, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024.