Effect of Physiologic Insulin Administration on Cognition

NCT06424652 | Completed

• 1 other identifier: PBRC 2024-014
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

In humans, insulin is secreted in pulses from the pancreatic beta-cells, and these oscillations help to maintain fasting plasma glucose levels within a narrow normal range. These pulses become disrupted in the presence of insulin resistance. Some people have referred to Alzheimer's Disease as type 3 diabetes because the glucose uptake in the brain is reduced by 30%. Clinical observations in clinics that treat patients with insulin pulses every 5 minutes for 3 hours twice a week for 2 weeks followed by once a week for 6 weeks and followed by less frequency treatments suggest an improvement in type 2 diabetes control, reduction in insulin resistance and an improvement in diabetes complications. A patient with Parkinson's Disease was treated with this pulsed insulin paradigm and experienced dramatic improvement that has now been maintained over years. Parkinson's Disease has been reported to have a decreased glucose uptake in the brain, so pulsed insulin treatment was tried in a small number of patients with Alzheimer's Disease and there was an impression that they showed improvement. Clinics that use pulsed insulin treatment change more than one parameter of the insulin pulses which makes it difficult to determine what is giving the improvement. The euglycemic hyper-insulinemic clamp, also called a clamp, is a well-standardized test that measures insulin resistance and involves intravenous insulin infusion. This single patient study will enroll one patient with early Alzheimer's disease and insulin resistance. The subject will have one standard clamp test with continuous insulin followed by 4 clamps over a 2-week period using the same amount of insulin over the same period of time but administered in pulses every 5 minutes. This was the number of pulsed insulin treatments needed to see a dramatic improvement in Parkinson's disease. The cognition in the Alzheimer's disease patient will be thoroughly evaluated with questionnaires and walking on a special mat while doing arithmetic tasks before and after the 4 pulsed insulin clamps. If this study demonstrates an improvement in cognition, one will know that the only thing that changed from the standard clamp was the pulse nature of the insulin delivery.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Effect of tissue sensitivity to insulin

  To determine the effect of tissue sensitivity to insulin delivered in pulses compared to insulin delivered continuously during the hyperinsulinemic euglycemic clamp test (clamp). The hypothesis is that delivery of insulin in pulses during the clamp (pulsatile clamp) will increase glucose disposal rate (GDR) compared to continuous delivery during the clamp (continuous clamp). To test the hypothesis, we will measure GDR during one pulsatile clamp and one continuous clamp at 40mU/m2/min insulin infusion.

  Two weeks

Secondary Outcomes (1)

• Effect of the pulsatile clamp at 40mU/m2/min insulin infusion on signs and symptoms of Alzheimer's disease

  Two weeks

Study Arms (1)

Single Participant with Evidence of cognitive impairment.

OTHER

Other: Blood draws; Other: Hyperinsulinemic Euglycemic Clamp Technique Insulin Sensitivity test; Other: Resting Metabolic Rate (RMR)

Interventions

Blood draws OTHER

After passing the screening, participation in the research study will be approximately three weeks. The participant will have seven study visits all at the Pennington Center. On five occasions, the participant will have a five-hour visit in the inpatient unit. At the study visit blood will be drawn. The total amount of blood drawn during the study is approximately 12 fluid ounces.

Single Participant with Evidence of cognitive impairment.

Hyperinsulinemic Euglycemic Clamp Technique Insulin Sensitivity test OTHER

This procedure measures how the body responds to insulin. Insulin is normally produced by the body during meals and helps the body use sugar. There will be two IV lines, one in the participant's arm and one in the participant's hand on the opposite side. Small amounts of glucose and insulin will be infused into the participant's arm. The participant's blood sugar level will be checked every 5-10 minutes from the IV in the hand to determine how much glucose the participant should have to keep blood sugar at a normal level. The participant's hand will be placed inside a warming box to increase skin temperature to about 105 degrees Fahrenheit. The temperature will be warm, but not uncomfortable. During the IV procedure, a small amount of the participant's own blood (less than 1 teaspoon) will immediately be returned into the vein through the IV after each specimen is collected.

Single Participant with Evidence of cognitive impairment.

Resting Metabolic Rate (RMR) OTHER

After the participant rests for 30 minutes, a clear plastic hood will be placed over the participant's head and chest area. The hood is ventilated with fresh air. The participant's oxygen intake and carbon dioxide output will be measured for 30 minutes to determine how many calories the participant burns during the time they are being tested.

Single Participant with Evidence of cognitive impairment.

Eligibility Criteria

• Age: 65 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Early Alzheimer's Disease
• Insulin Resistance

You may not qualify if:

• Inability to walk
• Unable to read, understand or inability to complete questionnaire
• Belong to a vulnerable group like prisoners

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead

Study Sites (1)

Penningto Biomedical Research Center

Baton Rouge, Louisiana, 70809, United States

Location

Related Publications (11)

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  PMID: 23968694 RESULT

• Leclerc M, Bourassa P, Tremblay C, Caron V, Sugere C, Emond V, Bennett DA, Calon F. Cerebrovascular insulin receptors are defective in Alzheimer's disease. Brain. 2023 Jan 5;146(1):75-90. doi: 10.1093/brain/awac309.

  PMID: 36280236 RESULT

• Cull O, Al Qadi L, Stadler J, Martin M, El Helou A, Wagner J, Maillet D, Chamard-Witkowski L. Radiological markers of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection: a mini-review. Front Neurol. 2023 Nov 24;14:1233079. doi: 10.3389/fneur.2023.1233079. eCollection 2023.

  PMID: 38073629 RESULT

• Chun MY, Chung SJ, Kim SH, Park CW, Jeong SH, Lee HS, Lee PH, Sohn YH, Jeong Y, Kim YJ. Hippocampal Perfusion Affects Motor and Cognitive Functions in Parkinson Disease: An Early Phase 18 F-FP-CIT Positron Emission Tomography Study. Ann Neurol. 2024 Feb;95(2):388-399. doi: 10.1002/ana.26827. Epub 2023 Nov 28.

  PMID: 37962393 RESULT

• Zhang Q, Fan C, Wang L, Li T, Wang M, Han Y, Jiang J; Alzheimer's Disease Neuroimaging Initiative. Glucose metabolism in posterior cingulate cortex has supplementary value to predict the progression of cognitively unimpaired to dementia due to Alzheimer's disease: an exploratory study of 18F-FDG-PET. Geroscience. 2024 Feb;46(1):1407-1420. doi: 10.1007/s11357-023-00897-0. Epub 2023 Aug 23.

  PMID: 37610594 RESULT

• Kapogiannis D, Boxer A, Schwartz JB, Abner EL, Biragyn A, Masharani U, Frassetto L, Petersen RC, Miller BL, Goetzl EJ. Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease. FASEB J. 2015 Feb;29(2):589-96. doi: 10.1096/fj.14-262048. Epub 2014 Oct 23.

  PMID: 25342129 RESULT

• Tam CS, Xie W, Johnson WD, Cefalu WT, Redman LM, Ravussin E. Defining insulin resistance from hyperinsulinemic-euglycemic clamps. Diabetes Care. 2012 Jul;35(7):1605-10. doi: 10.2337/dc11-2339. Epub 2012 Apr 17.

  PMID: 22511259 RESULT

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 RESULT

• Lin JS, O'Connor E, Rossom RC, Perdue LA, Burda BU, Thompson M, Eckstrom E. Screening for Cognitive Impairment in Older Adults: An Evidence Update for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Nov. Report No.: 14-05198-EF-1. Available from http://www.ncbi.nlm.nih.gov/books/NBK174643/

  PMID: 24354019 RESULT

• Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.

  PMID: 11556941 RESULT

• Feng YS, Kohlmann T, Janssen MF, Buchholz I. Psychometric properties of the EQ-5D-5L: a systematic review of the literature. Qual Life Res. 2021 Mar;30(3):647-673. doi: 10.1007/s11136-020-02688-y. Epub 2020 Dec 7.

  PMID: 33284428 RESULT

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Blood Specimen Collection; Basal Metabolism

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Energy Metabolism; Metabolism

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor-Chief Medical Officer

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 22, 2024
• Study Start: May 16, 2024
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: July 1, 2025
• Access Criteria: According to the Nutrition Obesity Research Center Protocol for sharing

Locations

US (1)