Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The SNIFF Device study will involve using a device to administer insulin through each participant's nose or intra-nasally. Insulin is a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. This study is measuring how much insulin the device delivers. In addition, this study will look at the effects of insulin or placebo administered intra-nasally using a nebulizer-like device on memory, blood, and cerebral spinal fluid.
The aim of this study is to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF).
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.
The study will consist of a single site, randomized, double-blind trial comparing the acute effects of INI (20 International Units) or placebo delivered with nebulizer-like device on CSF insulin levels, AD biomarkers and memory. At study entry, participants will be randomized to receive either an acute dose of insulin or placebo first, and the other substance on a second visit. Participants who are cognitively normal or who have aMCI (n=30) will be enrolled. The primary outcome measure will be to test the hypothesis that CSF insulin levels will increase 30 minutes after receiving a 20 International Units dose of insulin delivered with a nebulizer-like device, compared to levels achieved 30 minutes after placebo.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin first, then placebo | Experimental | Participants will be randomly assigned to receive regular insulin (U100, 20 IU) administered with an intranasal nebulizer-like device. Participants in this arm will then receive placebo at visit 3 during second intervention period. |
|
| Placebo first, then insulin | Experimental | Participants will be randomly assigned to receive placebo administered with an intranasal nebulizer-like device. At visit 3 during second intervention period, participants in this arm will receive insulin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin | Drug | 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company) |
|
| Measure | Description | Time Frame |
|---|---|---|
| CSF Insulin Levels | Levels of insulin in cerebrospinal fluid after being delivered with the device. This will help to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF) | 30 minutes after intervention administration |
| Measure | Description | Time Frame |
|---|---|---|
| The Auditory-Verbal Learning Test (AVLT) | memory measure in which participant hears a list of 12 words over 3 trials, and is asked to recall them immediately after hearing them, then again after a 45 minute delay. Total possible score is 36 for immediate recall and 12 for delayed recall. Higher scores are better. | 5 minutes before lumbar puncture, and immediately following lumbar puncture |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Suzanne Craft, PhD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21514249 | Background | Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21. | |
| 3758265 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The insulin-placebo/placebo-insulin sequence is a critical component of the study. It was counterbalanced in order to address potential practice effects for the Auditory-Verbal Learning Test (AVLT).
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Insulin First, Then Placebo | Participants in one group will receive regular insulin administered with an intranasal nebulizer-like device and will crossover to placebo for the second half of the trial. Participants in the other group will receive placebo first and crossover to insulin for the second half of the trail. Crossover occurs at visit 3. The insulin-placebo/placebo-insulin sequence is a critical component of the study. It was counterbalanced in order to address potential practice effects for the Auditory-Verbal Learning Test (AVLT). It is well known that memory test scores are lower the first time the test is taken, and then are higher the second time. The phenomenon is known as the practice effect. They are higher the second time because participants have been exposed to the memory stimuli previously. Thus if placebo is always administered first and insulin second, it may appear that the memory scores have improved due to the insulin, when the improvement is due instead to practice effects. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 |
| FG001 | Placebo First, Then Insulin | Participants in one group will receive regular insulin administered with an intranasal nebulizer-like device and will crossover to placebo for the second half of the trial. Participants in the other group will receive placebo first and crossover to insulin for the second half of the trail. Crossover occurs at visit 3. The insulin-placebo/placebo-insulin sequence is a critical component of the study. It was counterbalanced in order to address potential practice effects for the Auditory-Verbal Learning Test (AVLT). It is well known that memory test scores are lower the first time the test is taken, and then are higher the second time. The phenomenon is known as the practice effect. They are higher the second time because participants have been exposed to the memory stimuli previously. Thus if placebo is always administered first and insulin second, it may appear that the memory scores have improved due to the insulin, when the improvement is due instead to practice effects. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Participants in one group will receive regular insulin administered with an intranasal nebulizer-like device and will crossover to placebo for the second half of the trial. Participants in the other group will receive placebo first and crossover to insulin for the second half of the trail. Crossover occurs at visit 3. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | CSF Insulin Levels | Levels of insulin in cerebrospinal fluid after being delivered with the device. This will help to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF) | The insulin-placebo/placebo-insulin sequence is a critical component of the study. The order was counterbalanced to address a phenomenon known as Practice Effect when giving the AVLT. When memory test are given a second time scores are higher because participants have been exposed to the memory stimuli previously. Thus if placebo is always given first and insulin second, it may appear that the memory scores have improved due to the insulin when the improvement is due instead to Practice Effects. | Posted | Mean | Full Range | microUnits/mL | 30 minutes after intervention administration |
|
Up to Week 6
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Insulin | Participants will be randomly assigned to receive regular insulin (U100, 20 IU) administered with an intranasal nebulizer-like device. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company) intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| vasovagal episode | Nervous system disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Suzanne Craft, PhD | Atrium Health Wake Forest | 336-713-8846 | suzcraft@wakehealth.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 7, 2020 | Apr 8, 2025 | Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Sep 20, 2023 | Jan 30, 2025 | ICF_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
Not provided
Not provided
At study entry, participants will be randomized to receive either an acute dose of insulin or of placebo first and the other substance on a second visit.
Not provided
Not provided
Neither participants or site personnel will know whether insulin or saline is being administered. Exceptions will be the study nurse who is directly involved in preparing the insulin or placebo, as well as preparing DSMB reports.
| Placebo | Other | Matching placebo (sterile saline) to 20 IU Humulin® R U-100 |
|
|
| intranasal nebulizer-like device | Device | Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device. |
|
| CSF Levels of AB42 | Levels of the 42 amino acid isoform of the beta amyloid peptide | 30 minutes after intervention administration |
| CSF Levels of Total Tau | Levels of the tau protein | 30 minutes after intervention administration |
| CSF Levels Phospho-tau 181 | Levels of the tau phosphorylated at isotope 181 | 30 minutes after intervention administration |
| Background |
| Baker H, Spencer RF. Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Exp Brain Res. 1986;63(3):461-73. doi: 10.1007/BF00237470. |
| 20837822 | Background | Baker 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. |
| 3782501 | Background | Balin BJ, Broadwell RD, Salcman M, el-Kalliny M. Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. J Comp Neurol. 1986 Sep 8;251(2):260-80. doi: 10.1002/cne.902510209. |
| 15288712 | Background | Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W. Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004 Nov;29(10):1326-34. doi: 10.1016/j.psyneuen.2004.04.003. |
| 18230654 | Background | Benedict C, Kern W, Schultes B, Born J, Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab. 2008 Apr;93(4):1339-44. doi: 10.1210/jc.2007-2606. Epub 2008 Jan 29. |
| Background | Bodian, D. and H. A. Howe (1941). |
| 11992114 | Background | Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002 Jun;5(6):514-6. doi: 10.1038/nn849. No abstract available. |
| 2418083 | Background | Broadwell RD, Balin BJ. Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo. J Comp Neurol. 1985 Dec 22;242(4):632-50. doi: 10.1002/cne.902420410. |
| 16399806 | Background | Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006 Mar;129(Pt 3):564-83. doi: 10.1093/brain/awl004. Epub 2006 Jan 6. |
| 18549783 | Background | Chiu SL, Chen CM, Cline HT. Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron. 2008 Jun 12;58(5):708-19. doi: 10.1016/j.neuron.2008.04.014. |
| 21911655 | Background | 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. |
| 9443474 | Background | Craft 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. |
| 14980532 | Background | Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol. 2004 Mar;3(3):169-78. doi: 10.1016/S1474-4422(04)00681-7. |
| 19188609 | Background | De Felice FG, Vieira MN, Bomfim TR, Decker H, Velasco PT, Lambert MP, Viola KL, Zhao WQ, Ferreira ST, Klein WL. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1971-6. doi: 10.1073/pnas.0809158106. Epub 2009 Feb 2. |
| Background | Faber, H. K. (1938). |
| Background | Fairbrother, R. W. and E. W. Hurst (1930). |
| 16216936 | Background | 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. |
| 19015157 | Background | Francis GJ, Martinez JA, Liu WQ, Xu K, Ayer A, Fine J, Tuor UI, Glazner G, Hanson LR, Frey WH 2nd, Toth C. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain. 2008 Dec;131(Pt 12):3311-34. doi: 10.1093/brain/awn288. Epub 2008 Nov 16. |
|
| 9720972 | Background | Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Turk A, Hoyer S, Zochling R, Boissl KW, Jellinger K, Riederer P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm (Vienna). 1998;105(4-5):423-38. doi: 10.1007/s007020050068. |
| 9236950 | Background | Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9. |
| 11306609 | Background | Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, Xu H. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci. 2001 Apr 15;21(8):2561-70. doi: 10.1523/JNEUROSCI.21-08-02561.2001. |
| 20847404 | Background | Gil-Bea FJ, Solas M, Solomon A, Mugueta C, Winblad B, Kivipelto M, Ramirez MJ, Cedazo-Minguez A. Insulin levels are decreased in the cerebrospinal fluid of women with prodomal Alzheimer's disease. J Alzheimers Dis. 2010;22(2):405-13. doi: 10.3233/JAD-2010-100795. |
| 17848936 | Background | Hallschmid M, Benedict C, Schultes B, Born J, Kern W. Obese men respond to cognitive but not to catabolic brain insulin signaling. Int J Obes (Lond). 2008 Feb;32(2):275-82. doi: 10.1038/sj.ijo.0803722. Epub 2007 Sep 11. |
| 9235959 | Background | Hong M, Lee VM. Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons. J Biol Chem. 1997 Aug 1;272(31):19547-53. doi: 10.1074/jbc.272.31.19547. |
| 7104545 | Background | Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982 Jun;140:566-72. doi: 10.1192/bjp.140.6.566. |
| 12547019 | Background | Illum L. Nasal drug delivery: new developments and strategies. Drug Discov Today. 2002 Dec 1;7(23):1184-9. doi: 10.1016/s1359-6446(02)02529-1. |
| 10078556 | Background | Kern W, Born J, Schreiber H, Fehm HL. Central nervous system effects of intranasally administered insulin during euglycemia in men. Diabetes. 1999 Mar;48(3):557-63. doi: 10.2337/diabetes.48.3.557. |
| 5126829 | Background | Kristensson K, Olsson Y. Uptake of exogenous proteins in mouse olfactory cells. Acta Neuropathol. 1971;19(2):145-54. doi: 10.1007/BF00688493. No abstract available. |
| 12951650 | Background | Kupila A, Sipila J, Keskinen P, Simell T, Knip M, Pulkki K, Simell O. Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults. Diabetes Metab Res Rev. 2003 Sep-Oct;19(5):415-20. doi: 10.1002/dmrr.397. |
| 17692997 | Background | Lee CC, Kuo YM, Huang CC, Hsu KS. Insulin rescues amyloid beta-induced impairment of hippocampal long-term potentiation. Neurobiol Aging. 2009 Mar;30(3):377-87. doi: 10.1016/j.neurobiolaging.2007.06.014. Epub 2007 Aug 10. |
| 7622680 | Background | Minoshima S, Frey KA, Foster NL, Kuhl DE. Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr. 1995 Jul-Aug;19(4):541-7. doi: 10.1097/00004728-199507000-00006. |
| 8071705 | Background | Minoshima S, Koeppe RA, Frey KA, Kuhl DE. Anatomic standardization: linear scaling and nonlinear warping of functional brain images. J Nucl Med. 1994 Sep;35(9):1528-37. |
| 9191756 | Background | Morris JC, Ernesto C, Schafer K, Coats M, Leon S, Sano M, Thal LJ, Woodbury P. Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's Disease Cooperative Study experience. Neurology. 1997 Jun;48(6):1508-10. doi: 10.1212/wnl.48.6.1508. |
| 11735772 | Background | Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B. Current concepts in mild cognitive impairment. Arch Neurol. 2001 Dec;58(12):1985-92. doi: 10.1001/archneur.58.12.1985. |
| 6800439 | Background | Pontiroli AE, Alberetto M, Secchi A, Dossi G, Bosi I, Pozza G. Insulin given intranasally induces hypoglycaemia in normal and diabetic subjects. Br Med J (Clin Res Ed). 1982 Jan 30;284(6312):303-6. doi: 10.1136/bmj.284.6312.303. |
| 15964100 | Background | 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. |
| 18430999 | Background | Reger MA, Watson GS, Green PS, Baker LD, Cholerton B, Fishel MA, Plymate SR, Cherrier MM, Schellenberg GD, Frey WH 2nd, Craft S. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J Alzheimers Dis. 2008 Apr;13(3):323-31. doi: 10.3233/jad-2008-13309. |
| 17942819 | Background | Reger 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. |
| 16340083 | Background | Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J Alzheimers Dis. 2005 Dec;8(3):247-68. doi: 10.3233/jad-2005-8304. |
| Background | Rubin, D. B. (1987). Multiple Imputation for Nonresponse in Surveys. Hoboken, New Jersey, John Wiley & Sons, Inc |
| 7494186 | Background | Sakane T, Akizuki M, Taki Y, Yamashita S, Sezaki H, Nadai T. Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the molecular weight of drugs. J Pharm Pharmacol. 1995 May;47(5):379-81. doi: 10.1111/j.2042-7158.1995.tb05814.x. |
| 20921876 | Background | Sano M, Raman R, Emond J, Thomas RG, Petersen R, Schneider LS, Aisen PS. Adding delayed recall to the Alzheimer Disease Assessment Scale is useful in studies of mild cognitive impairment but not Alzheimer disease. Alzheimer Dis Assoc Disord. 2011 Apr-Jun;25(2):122-7. doi: 10.1097/WAD.0b013e3181f883b7. |
| 18359102 | Background | Selkoe DJ. Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res. 2008 Sep 1;192(1):106-13. doi: 10.1016/j.bbr.2008.02.016. Epub 2008 Feb 17. |
| 3840049 | Background | Shipley MT. Transport of molecules from nose to brain: transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Res Bull. 1985 Aug;15(2):129-42. doi: 10.1016/0361-9230(85)90129-7. |
| 15501490 | Background | Stockhorst U, de Fries D, Steingrueber HJ, Scherbaum WA. Insulin and the CNS: effects on food intake, memory, and endocrine parameters and the role of intranasal insulin administration in humans. Physiol Behav. 2004 Oct 30;83(1):47-54. doi: 10.1016/j.physbeh.2004.07.022. |
| 8548316 | Background | Thorne RG, Emory CR, Ala TA, Frey WH 2nd. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res. 1995 Sep 18;692(1-2):278-82. doi: 10.1016/0006-8993(95)00637-6. |
| 15262337 | Background | Thorne RG, Pronk GJ, Padmanabhan V, Frey WH 2nd. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience. 2004;127(2):481-96. doi: 10.1016/j.neuroscience.2004.05.029. |
| 17855343 | Background | Townsend M, Mehta T, Selkoe DJ. Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway. J Biol Chem. 2007 Nov 16;282(46):33305-33312. doi: 10.1074/jbc.M610390200. Epub 2007 Sep 13. |
| 16591462 | Background | Weiss P, Holland Y. Neuronal dynamics and axonal flow, ii. The olfactory nerve as model test object. Proc Natl Acad Sci U S A. 1967 Feb;57(2):258-64. doi: 10.1073/pnas.57.2.258. No abstract available. |
| 1400644 | Background | Worsley KJ, Evans AC, Marrett S, Neelin P. A three-dimensional statistical analysis for CBF activation studies in human brain. J Cereb Blood Flow Metab. 1992 Nov;12(6):900-18. doi: 10.1038/jcbfm.1992.127. |
| 15590928 | Background | Zhao L, Teter B, Morihara T, Lim GP, Ambegaokar SS, Ubeda OJ, Frautschy SA, Cole GM. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J Neurosci. 2004 Dec 8;24(49):11120-6. doi: 10.1523/JNEUROSCI.2860-04.2004. |
| 19026743 | Background | Zhao WQ, Townsend M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease. Biochim Biophys Acta. 2009 May;1792(5):482-96. doi: 10.1016/j.bbadis.2008.10.014. Epub 2008 Nov 5. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Placebo First, Then Insulin | Participants will be randomly assigned to receive placebo administered with an intranasal nebulizer-like device. At visit 3 during second intervention period, participants in this arm will receive insulin. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device. |
|
|
| Secondary | The Auditory-Verbal Learning Test (AVLT) | memory measure in which participant hears a list of 12 words over 3 trials, and is asked to recall them immediately after hearing them, then again after a 45 minute delay. Total possible score is 36 for immediate recall and 12 for delayed recall. Higher scores are better. | The insulin-placebo/placebo-insulin sequence is a critical component of the study. The order was counterbalanced to address a phenomenon known as Practice Effect when giving the AVLT. When memory test are given a second time scores are higher because participants have been exposed to the memory stimuli previously. Thus if placebo is always given first and insulin second, it may appear that the memory scores have improved due to the insulin when the improvement is due instead to Practice Effects. | Posted | Mean | Full Range | average words recalled | 5 minutes before lumbar puncture, and immediately following lumbar puncture |
|
|
|
| Secondary | CSF Levels of AB42 | Levels of the 42 amino acid isoform of the beta amyloid peptide | The insulin-placebo/placebo-insulin sequence is a critical component of the study. The order was counterbalanced to address a phenomenon known as Practice Effect when giving the AVLT. When memory test are given a second time scores are higher because participants have been exposed to the memory stimuli previously. Thus if placebo is always given first and insulin second, it may appear that the memory scores have improved due to the insulin when the improvement is due instead to Practice Effects. | Posted | Mean | Full Range | pg/ml | 30 minutes after intervention administration |
|
|
|
| Secondary | CSF Levels of Total Tau | Levels of the tau protein | The insulin-placebo/placebo-insulin sequence is a critical component of the study. The order was counterbalanced to address a phenomenon known as Practice Effect when giving the AVLT. When memory test are given a second time scores are higher because participants have been exposed to the memory stimuli previously. Thus if placebo is always given first and insulin second, it may appear that the memory scores have improved due to the insulin when the improvement is due instead to Practice Effects. | Posted | Mean | Full Range | pg/ml | 30 minutes after intervention administration |
|
|
|
| Secondary | CSF Levels Phospho-tau 181 | Levels of the tau phosphorylated at isotope 181 | The insulin-placebo/placebo-insulin sequence is a critical component of the study. The order was counterbalanced to address a phenomenon known as Practice Effect when giving the AVLT. When memory test are given a second time scores are higher because participants have been exposed to the memory stimuli previously. Thus if placebo is always given first and insulin second, it may appear that the memory scores have improved due to the insulin when the improvement is due instead to Practice Effects. | Posted | Mean | Full Range | pg/ml | 30 minutes after intervention administration |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 4 |
| 20 |
| EG001 | Placebo | Participants will be randomly assigned to receive placebo administered with an intranasal nebulizer-like device. Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device. | 0 | 20 | 0 | 20 | 0 | 20 |
| low back discomfort | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| tired | General disorders | Systematic Assessment |
|
| rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| First Intervention Immediately following lumbar puncture |
|
|
| Second Intervention 5 minutes before lumbar puncture |
|
|
| Second Intervention Immediately following lumbar puncture |
|
|
| Placebo first, then insulin |
|
|
| Placebo first, then insulin |
|
|
| Placebo first, then insulin |
|
|