Establish Diagnostic Models Based on Olfactory Function and Odor-induced Brain Activation for Diabetes-Related Cognitive Impairment

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Cross-sectional and Longitudinal Study to Establish Diagnostic Models Based on Olfactory Function and Odor-induced Brain Activation for Diabetes-Related Cognitive Impairment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05543967
• Other study ID #: 2022-LCYJ-PY-15
• Status: Recruiting
• Start date: October 18, 2022
• Est. completion date: August 31, 2025

Study information

• Verified date: August 2022
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Wen Zhang, MD, PhD
• Phone: 86-15950576908
• Email: zw7830254[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a cross-sectional and longitudinal study to establish diagnostic models based on olfactory function assessments and odor-induced brain activation for cognitive impairment in patients with type 2 diabetes mellitus.

Description:

Patients with diabetes have increased risks of cognitive impairment and dementia, which affecting the quality of life and diabetes management. Therefore, it is an urgent challenge to identify non-invasive biomarkers for early diagnosis and prognosis of the cognitive decline in patients with diabetes. Previous research has shown that both olfactory dysfunction and decreased odor-induced brain activation are present before clinically measurable cognitive decrements in type 2 diabetes. This is a cross-sectional and longitudinal study to establish diagnostic models based on olfactory function assessments and odor-induced brain activation for cognitive impairment in patients with type 2 diabetes mellitus. The investigators will recruit 200 patients with type 2 diabetes in the outpatient and inpatient departments. Health controls will be recruited from the community. At the baseline, clinical information collection, 100g-steamed bread meal test, biochemical measurement, cognitive assessments, olfactory test and functional magnetic resonance imaging(fMRI) scan will be conducted for all participants. Study duration was 3 years with a follow-up every 18 months. In the longitudinal study, all of the assessments will be repeated to evaluate changes of observational parameters.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: August 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Aged 40-75 years

• Right handedness

• Possessed over 6-year education

• Provision of informed consent prior to any study specific procedures

• Disease duration of T2DM patients >1 year

Exclusion Criteria:

• Control participants would be excluded if they had a fasting blood glucose level >7.0 mmol/L; glucose level> 7.8 mmol/L after oral glucose tolerance test (OGTT); HbA1c>5.7%

• Control participants would be excluded if they had a Montreal Cognitive Assessment (MoCA, Beijing edition) score of < 26

• Any acute disease

• History of neurologic or psychological illness

• Abnormal results of thyroid hormones, vitamin B12, and folate

• Metal implants, unable to complete the MR scanning

• Partial or complete olfactory dysfunction associated with sinusitis, allergic rhinitis, and deviated nasal septum

• Pregnant or lactating women

• Participating in other clinical trials at the same time or within 6 months prior to the start of the trial

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Cognitive Impairment
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Behavioral:
• Cognitive assessments
Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Boston Naming Test (BNT), Digit Span Test (DST), Trail Making Test (TMT).

Other:
• Olfactory function measurements
Olfactory Threshold, Odor Identification Score, Odor Memory Score.
• Functional magnetic resonance imaging
resting-state fMRI, odor-induced fMRI.

Locations

Country	Name	City	State
China	Department of Radiology, the Affiliated Drum Tower Hospital of Nanjing University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline cognitive performance	The Montreal Cognitive Assessment (MoCA) score, ranges from 0 to 30, and higher scores mean better cognition.	Day 1 of entry study
Primary	Baseline olfactory threshold	Olfactory threshold test: score range 1-13.5, which is determined based on a series of binary dilutions of the N-butanol solution in light mineral oil. The higher the score is, the more sensitive the participant is in detecting an odor. Scores of 8-10 were considered normal olfactory sensitivity, whereas scores of 1-3 signified olfactory dysfunction or anosmia, and scores of =10 indicate better olfactory sensitivity.	Day 1 of entry study
Primary	Baseline olfactory memory	Olfactory memory test: Part A: Participants are shown 4 pictures for each odor (10 odors in total), then they need to select what they sniffed. Have a 10-minute break. Part B: Participants sniff 20 different odors, 10 of which are the same odors as in Part A. They need to select the picture and figure out whether the odor is old or new.	Day 1 of entry study
Primary	Baseline odor-induced brain fMRI activation	Each participant underwent a series of task fMRI scans to measure temporal brain response to four increasing concentrations of lavender odors (0.032%, 0.10%, 0.32%, and 1.0) diluted in 1,2-propanediol (Sigma-Aldrich, St. Louis, MO). The visual cues of "+" and "smell" were used for baseline and odor stimulation, respectively. Each concentration was assessed three times, with fresh air and scent occurring alternately. Participants were instructed to press a button once they smelled the lavender scent. A general linear model was used to estimate odor-induced brain activation. Contrasts between "fresh air > rest" and "scent > rest" for each participant were made to get odor-induced brain activation value. Bilateral parahippocampus, amygdala, piriform cortex, insula, orbitofrontal cortex, entorhinal cortex, and hippocampus were extracted and merged as olfactory regions of interest (ROIs) for further analyses.	Within 1 week after cognitive assessments
Primary	Longitudinal changes of cognitive performance	Compare the change of MoCA score from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up). The Montreal Cognitive Assessment (MoCA) score, ranges from 0 to 30, and higher scores mean better cognition.	From baseline to 18 months' follow-up and 36 months' follow-up
Primary	Longitudinal changes of olfactory threshold	Compare the change of olfactory threshold tests score from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up). Olfactory threshold test: score range 1-13.5, which is determined based on a series of binary dilutions of the N-butanol solution in light mineral oil. The higher the score is, the more sensitive the participant is in detecting an odor. Scores of 8-10 were considered normal olfactory sensitivity, whereas scores of 1-3 signified olfactory dysfunction or anosmia, and scores of =10 indicate better olfactory sensitivity.	From baseline to 18 months' follow-up and 36 months' follow-up
Primary	Longitudinal changes of olfactory memory	Compare the change of olfactory memory tests score from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up). Olfactory memory test: Part A: Participants are shown 4 pictures for each odor (10 odors in total), then they need to select what they sniffed. Have a 10-minute break. Part B: Participants sniff 20 different odors, 10 of which are the same odors as in Part A. They need to select the picture and figure out whether the odor is old or new.	From baseline to 18 months' follow-up and 36 months' follow-up
Primary	Longitudinal changes of odor-induced brain fMRI activation	Compare the change of odor-induced brain activation beta value from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up)	From baseline to 18 months' follow-up and 36 months' follow-up
Secondary	Baseline brain structural MRI scan	Cortical morphology	Within 1 week after cognitive assessments
Secondary	Baseline brain functional MRI scan	Large-scale network functional connectivity	Within 1 week after cognitive assessments
Secondary	Longitudinal changes of brain structural MRI scan	Compare the change of cortical morphology from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up)	From baseline to 18 months' follow-up and 36 months' follow-up
Secondary	Longitudinal changes of functional MRI scan	Compare the change of large-scale network functional connectivity from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up)	From baseline to 18 months' follow-up and 36 months' follow-up