Clinical trial NCT05372458: The Mechanism Study of Diabetic Pancreatic Amyloid Deposition on Cognitive Dysfunction in Alzheimer's Disease
Official title: The Mechanism Study of Diabetic Pancreatic Amyloid Deposition on Cognitive
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: AD
DM
PET-CT
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2022-05-12
Enrollment: 400
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: clinical or community

Brief summary: Alzheimer's disease (AD) is closely related to diabetes (DM). DM will aggravate the progression of AD, but the specific mechanism has not yet been clarified. Previous study found that a key pathological feature of the pancreas in patients with DM is islet amyloid polypeptide, and there is also islet amyloid polypeptide in the brain. Therefore, DM may cause cytotoxicity through the interaction between pancreatic amyloid and brain Aβ protein and further aggravate AD progress. In this study, starting with DM and AD pathological biomarkers, the amyloid PET target molecular probe 18F-AV45 will be used to monitor the dynamic changes of amyloid protein in the brain and pancreas during the development of AD. The completion of this study will provide a new view for understanding the mechanism of DM on AD cognitive dysfunction and effectively preventing and treating these two diseases.

Detailed description: This is a single-center, prospective, and observational study, which mainly focuses on the interaction between pancreatic amyloid and brain Aβ protein and further aggravates AD progress in China. PET imaging will be used on subjects. Previously collected patient data may also be enrolled in this study.

Eligibility criteria: Inclusion Criteria:

* Non-disease controls:

  1. Age between 60 and 80 years old; gender is not limited.
  2. The investigators have normal cognition and negative Aβ imaging through the test.
  3. Informed consent must be signed in writing by the subjects or their legal guardians and caregivers.
  4. Blood routine: white blood cell count (WBC) 4\~10×109/L; platelet (PLT) 100\~300×109/L; hemoglobin (HB) 120\~160 g/L; renal function: serum creatinine less than or equal to Upper limit of normal range; liver function: bilirubin, AST (SGOT)/ALT (SGPT) less than or equal to the upper limit of normal range; electrocardiogram: no significant abnormality.
  5. Willingness and ability to cooperate with all projects of this research.

AD patients/DM patients:

1. Age between 60 and 80 years old; gender is not limited.
2. The diagnosis of AD was based on the 2011 National Association on Aging and Alzheimer's Disease (NIA-AA) diagnostic criteria for possible AD dementia. The diagnostic criteria for diabetes were based on the 1999 World Health Organization (WHO) diagnostic criteria for diabetes.
3. Brain MRI supports the diagnosis of AD, and there is no evidence of other neurological diseases.
4. No neurological disease, major chronic disease, malignant tumor or acute infectious disease has been confirmed by the investigator.
5. An informed consent form must be signed in writing by the subjects or their legal guardians and caregivers.
6. Blood routine: white blood cell count (WBC) 4\~10×109/L; platelet (PLT) 100\~300×109/L; hemoglobin (HB) 120\~160 g/L; renal function: serum creatinine less than or equal to Upper limit of normal range; function: bilirubin, AST (SGOT)/ALT (SGPT) less than or equal to the upper limit of normal range; electrocardiogram: no significant abnormality.
7. Willingness and ability to cooperate with all projects of this research.

Exclusion Criteria:

* Subjects meeting any of the following criteria will be excluded from the study:

  1. Suffering from other serious neurological diseases, or gastrointestinal, cardiovascular, liver, kidney, blood system, tumor endocrine, respiratory system, immune deficiency and other serious diseases.
  2. Candidate subjects have contraindications to PET/CT scanning. Those who cannot accept repeated intravenous injections; those who may be allergic to drugs and their components (including a history of severe allergy or allergic reactions, especially those who are allergic to the tested drugs); phobia of tightness.
  3. In the past year, in addition to participating in the expected radiation exposure of this clinical study, have participated in other research programs or clinical care, resulting in radiation exposure exceeding the effective dose of 50 mSv.
  4. Drug or alcohol abuse for at least 1 month.
  5. The venous condition is poor and cannot tolerate repeated venipuncture.
  6. The candidate subject has received major surgery within the past 3 months; received experimental drug or device treatment (with unclear effect or safety) within 1 month
  7. The candidate subjects have any clinical conditions that the host of this study believes that this preparation may cause or have potential harm.

Primary outcomes:
measure: Complete PET imaging
timeFrame: 50mins from time of injection
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital
Study officials:
affiliation: Huashan Hospital
name: Fang Xie, PhD
role: PRINCIPAL_INVESTIGATOR
References: