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Exercise and Intranasal Insulin in Type 2 Diabetes

26 de junho de 2026 atualizado por: Steven K Malin, PhD, Rutgers, The State University of New Jersey

Effects of Intranasal Insulin Plus Exercise Training on Brain Blood Flow, Neuronal Insulin Signaling, and Cognition in Adults With Type 2 Diabetes

About 6.5 million adults in the United States who are 65 or older have dementia.

While the exact cause of dementia is not known, it may be due to changes in the brain. Further, risk may be higher when the brain does not respond to insulin. Indeed, brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise may help reduce the risk of dementia by increased blood flow to the brain and help the brain respond better to insulin. In addition, giving insulin through a nose spray (called intranasal insulin) may also help with thinking and memory. However, it is unknown if using both exercise and intranasal insulin is best for the brain.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

This goal of this study is to find out if exercise plus an insulin nose spray works better than exercise alone for brain blood flow in older adults with Type 2 Diabetes. This study will also look at how the brain uses insulin and thinking skills. Individuals will be randomized to one of two groups. One group will exercise and use an insulin nose spray. The other group will exercise and use a saline (placebo) nose spray. Exercise training will be supervised and consist of walking or light jogging 3 times per week for 16 weeks. Brain imaging, cognition, and blood tests will be conducted before and after the intervention. Other measures include fitness tests and body composition scans.

Tipo de estudo

Intervencional

Inscrição (Estimado)

60

Estágio

  • Fase 2
  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Estados Unidos
    • New Jersey
      • New Brunswick, New Jersey, Estados Unidos, 08901
        • Recrutamento
        • Rutgers University Loree Gymnasium
        • Contato:
      • New Brunswick, New Jersey, Estados Unidos, 08901
        • Recrutamento
        • Institute for Food, Nutrition, and Health
        • Contato:
      • New Brunswick, New Jersey, Estados Unidos, 08091
        • Recrutamento
        • Robert Wood Johnson University Hospital Clinical Research Center
        • Contato:
      • Piscataway, New Jersey, Estados Unidos, 08854
        • Recrutamento
        • Center for Advanced Human Brain Imaging Research
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria:

  • Male or female 55-80 years old
  • Type 2 diabetes diagnosis or confirmation HbA1c >6.5% and fasting glucose >126 mg/dl
  • Individuals prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IV inhibitors, Acarbose, SGLT-2 inhibitors >6 months.
  • MOCA ≥26
  • Body mass index (BMI) ≥25 and ≤40 kg/m2
  • Not diagnosed with Type 1 diabetes
  • Not currently engaged in <90 min/wk of exercise

Exclusion Criteria:

  • A diagnosis of dementia
  • Neurologic disease (e.g. Parkinson's, autonomic neuropathy, etc.)
  • Intolerance to insulin
  • Morbidly obese patients (BMI >40 kg/m2) and lean patients (BMI <25 kg/m2)
  • >2 kg weight change in past 6 months
  • Participants who have been recently active (>90 min of moderate/high intensity exercise)
  • Individuals who are smokers or who have quit smoking (<2 years)
  • Hypertriglyceridemia (400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
  • Uncontrolled Hypertensive (>160/100 mmHg)
  • Participants with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety
  • Pregnant (as evidenced by positive pregnancy test) or nursing women
  • Participants with contraindications to participation in an exercise training program
  • Major psychiatric disorders (e.g. psychosis, bipolar disorder, major depression, alcohol/substance abuse)
  • History of head trauma or loss of consciousness in last 5 years.

  • Known contraindications for MR imaging:

    • History of head trauma or neurosurgery, or neurological disorder (other than headaches or peripheral nerve disease) as these may impact neuroimaging results.
    • Ferrous material implanted in or on the body, including flakes or filings, surgical clips, bullets, or electrical devices such as a pacemaker, or nonremovable ferrous jewelry (fillings in teeth and permanent retainers are permitted).
    • Fillings and permanent retainers do not provide a safety risk and are not general exclusions. However, upper retainers may cause artifacts in ventral frontal regions and therefore may be an exclusion for some studies.
    • Individuals with surgical pins or plates above the neck are excluded. Surgical pins or plates below the neck are exclusions, except when the material is fixed to bone, and considered acceptable by the Reference Manual for Magnetic Resonance Safety. Implants and Devices, 2020 Edition. Almost all recent orthopedic implants are made of materials that are not ferromagnetic and therefore are safe for scanning, and even though some screws are still made of ferromagnetic materials these are firmly screwed into bone. In cases where the material is unknown or deemed unsafe for scanning by the Reference Manual for Magnetic Resonance Safety. Implants and Devices the participant will be excluded.
    • History of eye injury involving metallic materials, shavings in eyes, or welding without a face mask
    • Lead/iron tattoos
    • Claustrophobia (history of significant anxiety in closed places).
    • Back problem that would prevent the subject from laying still comfortably for up to 90 minutes.
    • Deafness

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador de Placebo: HiEx with Intranasal Placebo
Medicamento: Intranasal Placebo
Saline will be administered twice daily (20 seconds in each nostril) using the Kurve Technology intranasal insulin device.
Comportamental: High Intensity Exercise
High intensity exercise will consist of 16 weeks of walking at ~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk. The duration of each exercise session will be adjusted based on fitness level so that ~300 kcal will be expended per training session during weeks 1-2, 350 kcal per training session during weeks 3-4, and 400 kcal per training session during weeks 5-16. This usually equals ~60 minutes per session but can vary from person to person. Each session will start with a 5-minute warm-up and end with a 5-minute cool down. During each exercise session, individuals will wear a heart rate monitor rating of perceived exertion will be recorded.
Comparador Ativo: HiEx with Intranasal Insulin
Comportamental: High Intensity Exercise
High intensity exercise will consist of 16 weeks of walking at ~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk. The duration of each exercise session will be adjusted based on fitness level so that ~300 kcal will be expended per training session during weeks 1-2, 350 kcal per training session during weeks 3-4, and 400 kcal per training session during weeks 5-16. This usually equals ~60 minutes per session but can vary from person to person. Each session will start with a 5-minute warm-up and end with a 5-minute cool down. During each exercise session, individuals will wear a heart rate monitor rating of perceived exertion will be recorded.
Medicamento: Intranasal Insulin
Dosage will be 20 IU of INI twice per day (40 IU in total/day). The study will use the Kurve Technology intranasal device, which delivers a 20 second stream of insulin through a nose piece into a nostril, after which the device switches off. The process will then be repeated in the other nostril.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Cerebrovascular Insulin Sensitivity
Prazo: Change from baseline to the end of the intervention at 16 weeks

People will undergo a motion corrected diffusion weighted gradient-and spin echo pseudo-Continuous Arterial Spin Labeling (pCASL) sequence with 5 post labelling delays. This provides 3.5 mm3 resolution for whole brain coverage for CBF. CBF will be determined via the hippocampus.

Participants will then be administrated INI at a dose of 40 IU of human insulin (0.4 ml, Humulin, Eli Lilly & Co., Indianapolis, IN). Single puffs of 0.1ml will occur 4 times (twice each nostril) over 2 minutes via the VianaseTM electronic atomizers (Kurve Technology Inc., Lynnwood, WA). After 30 minutes, scanning will be repeated to determine CBF changes to indicate brain insulin sensitivity. Brain insulin sensitivity will be defined as the change from fasting to INI (e.g. CBFINI - CBFfast).
Change from baseline to the end of the intervention at 16 weeks

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Blood Brain Barrier Integrity
Prazo: Change from baseline to the end of the intervention at 16 weeks

People will undergo a motion corrected diffusion weighted gradient-and spin echo pseudo-Continuous Arterial Spin Labeling (pCASL) sequence with 5 post labelling delays. This provides 3.5 mm3 resolution for whole brain coverage for BBB water exchange (Kw). Kw will serve as primary index of BBB integrity.

Participants will then be administrated INI at a dose of 40 IU of human insulin (0.4 ml, Humulin, Eli Lilly & Co., Indianapolis, IN). Single puffs of 0.1ml will occur 4 times (twice each nostril) over 2 minutes via the VianaseTM electronic atomizers (Kurve Technology Inc., Lynnwood, WA). After 30 minutes, scanning will be repeated to determine BBB changes from fasting to INI (e.g. KwINI - Kwfast).
Change from baseline to the end of the intervention at 16 weeks
Insulin Signaling Proteins
Prazo: Change from baseline to the end of the intervention at 16 weeks

Insulin signaling proteins pIRS-1Ser636 and pAktSer473, derived from neuronal extracellular vesicles (nEVs) will be measured before and 30 minutes after intranasal insulin (e.g. nEVsINI - nEVsfast).

nEVs will be isolated from plasma samples through a 2-step method: 1) isolating total plasma nEVs via Size Exclusion Chromatography (SEC) and selective immunocapture targeting three neuronal-specific epitopes on intact EVs (L1CAM, NLGN3, and GAP43). Isolated nEVs concentration and size distribution will be assessed by nanoparticle tracking analysis (NTA). nEV concentration will be used to normalize protein biomarker values to account for differential recovery.
Change from baseline to the end of the intervention at 16 weeks
Augmentation Index
Prazo: Change from baseline to the end of the intervention at 16 weeks
Brachial artery augmentation index (AIx75) will be tested in the semi-supine position using the SphygmoCor device to depict arterial stiffness before and after INI (e.g. AIx75INI - AIx75fast).
Change from baseline to the end of the intervention at 16 weeks
Peripheral Insulin Sensitivity
Prazo: Change from baseline to the end of the intervention at 16 weeks
A 120 minute 75g OGTT will be used to depict insulin sensitivity.
Change from baseline to the end of the intervention at 16 weeks
Cognitive Function
Prazo: Change from baseline to the end of the intervention at 16 weeks
Cognitive function will be assessed via the NIH toolbox. The NIH toolbox is an iPad application that consists of cognitive, emotional, motor, and sensory function assessments. Specific measurements will include: Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, Pattern Comparison Processing Speed Test, and Picture Sequence Memory Test.
Change from baseline to the end of the intervention at 16 weeks
Pulse Wave Velocity
Prazo: Change from baseline to the end of the intervention at 16 weeks
Pulse Wave Velocity (PWV) will be tested in the semi-supine position using the SphygmoCor device to depict arterial stiffness before and after INI (i.e. PWV-INI - PWV-fast).
Change from baseline to the end of the intervention at 16 weeks
Insulin Secretion
Prazo: Change from baseline to the end of the intervention at 16 weeks
A 120 minute 75g OGTT will be used to depict insulin secretion. Using the oral c-peptide minimal model (OMM), an estimate of 3 insulin secretion patterns will be be obtained: 1) one that is proportional to glucose rate change (i.e. early phase); 2) another proportional to plasma glucose above a threshold after a delay (i.e. late phase); and 3) total responsivity index, (total phase).
Change from baseline to the end of the intervention at 16 weeks

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Rutgers, The State University of New Jersey

Colaboradores

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigadores

  • Investigador principal: Steven K Malin, PhD, Rutgers University - New Brunswick

Publicações e links úteis

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Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

3 de agosto de 2026

Conclusão Primária (Estimado)

18 de maio de 2029

Conclusão do estudo (Estimado)

31 de maio de 2029

Datas de inscrição no estudo

Enviado pela primeira vez

22 de junho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

26 de junho de 2026

Primeira postagem (Real)

30 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

30 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

26 de junho de 2026

Última verificação

1 de junho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • Pro2026000751
  • 1R01DK147509-01 (Concessão/Contrato do NIH dos EUA)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Não

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