NCT05543967

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Oct 2022

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 9, 2022

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 16, 2022

Completed
1 month until next milestone

Study Start

First participant enrolled

October 18, 2022

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2025

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2025

Completed
Last Updated

October 26, 2022

Status Verified

August 1, 2022

Enrollment Period

2.7 years

First QC Date

September 9, 2022

Last Update Submit

October 23, 2022

Conditions

Outcome Measures

Primary Outcomes (8)

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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 Outcomes (4)

  • Baseline brain structural MRI scan

    Within 1 week after cognitive assessments

  • Baseline brain functional MRI scan

    Within 1 week after cognitive assessments

  • Longitudinal changes of brain structural MRI scan

    From baseline to 18 months' follow-up and 36 months' follow-up

  • Longitudinal changes of functional MRI scan

    From baseline to 18 months' follow-up and 36 months' follow-up

Study Arms (2)

Type 2 Diabetes Mellitus

These patients must have a definite diagnosis of type 2 diabetes mellitus (T2DM) according to the American Diabetes Association (ADA) standards. Some of these patients have symptoms of cognitive impairment, while others have normal cognition. All T2DM patients will undergo physical exam, cognitive and olfactory test as well as structural and brain functional MRI at baseline and follow-up time points.

Behavioral: Cognitive assessmentsOther: Olfactory function measurementsOther: Functional magnetic resonance imaging

Healthy Control

These participants have normal glucose tolerance and normal cognition. All HC subjects will undergo physical exam, cognitive and olfactory test as well as structural and brain functional MRI at baseline and follow-up time points.

Behavioral: Cognitive assessmentsOther: Olfactory function measurementsOther: Functional magnetic resonance imaging

Interventions

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).

Healthy ControlType 2 Diabetes Mellitus

Olfactory Threshold, Odor Identification Score, Odor Memory Score.

Healthy ControlType 2 Diabetes Mellitus

resting-state fMRI, odor-induced fMRI.

Also known as: fMRI
Healthy ControlType 2 Diabetes Mellitus

Eligibility Criteria

Age40 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

T2DM patients will be recruited from the outpatient and inpatient units of the endocrinology department of the investigator's hospital. Healthy control will be recruited in the community.

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Radiology, the Affiliated Drum Tower Hospital of Nanjing University

Nanjing, Jiangsu, 210008, China

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesCognition DisordersNeurocognitive DisordersMental Disorders

Central Study Contacts

Wen Zhang, MD, PhD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 9, 2022

First Posted

September 16, 2022

Study Start

October 18, 2022

Primary Completion

June 30, 2025

Study Completion

August 31, 2025

Last Updated

October 26, 2022

Record last verified: 2022-08

Data Sharing

IPD Sharing
Will share

IPD sharing will be made during the 12 months after the end of study, and the original data can be obtained from the PI if necessary.

Shared Documents
STUDY PROTOCOL, SAP, ANALYTIC CODE
Time Frame
during the 12 months after the end of study

Locations