Benzodiazepine Impact on Cognitive Function: fNIRs and PET/MRI Study

Depression, Anxiety Clinical Trial

Official title:

Assessing the Cognitive Effects of Chronic Benzodiazepine Use in Patients: A Comprehensive Study Using fNIRs and PET/MRI Technologies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06250842
• Other study ID #: PJ-KS-KY-2023-577
• Status: Recruiting
• Start date: February 11, 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: January 2024
• Source: The First Affiliated Hospital of Dalian Medical University
• Contact: Hui min Zhang
• Phone: +86 18098876233
• Email: huiminzhangxs[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study explores the impact of long-term benzodiazepine (BZDs) use on cognitive function and associated neuroimaging markers. While BZDs are established treatments for conditions like anxiety and insomnia, recent warnings highlight risks, including neurocognitive effects. Neuroimaging studies indicate potential neuroprotective effects of BZDs. Functional near-infrared spectroscopy (fNIRS) measures cerebral cortex function during cognitive tasks. Combining fNIRS with mood and cognitive scales, this study assesses cortical activation. 2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) evaluates brain metabolism. DPA-714 PET assesses neuroinflammation. The primary objective is to compare brain functional activation, metabolism, and neuroinflammatory levels between long-term BZD users and non-users. This comprehensive approach aims to provide insights into BZD effects on cognition and associated brain markers.

Description:

Benzodiazepines(BZDs) have been long-established treatments for various conditions, including anxiety disorders and insomnia. Recent FDA warnings emphasize the risks of misuse and dependence associated with BZDs. Epidemiological investigations have consistently raised concerns regarding the long-term utilization of GABAergic medications, such as BZD and Z-drugs, due to their observed association with an elevated likelihood of neurocognitive impairments, including the development of Alzheimer's disease(AD). Recent neuroimaging studies have provided insights into the neuroprotective effects of BZD. These studies reveal that prolonged use of BZD in humans is associated with reduced amyloid deposition and a greater hippocampus volume. Functional near-infrared spectroscopic imaging utilizes changes in measured near-infrared light to monitor relative changes in oxyhemoglobin and deoxyhemoglobin concentrations in the cerebral cortex, allowing the detection of dynamic changes in cerebral cortical function during cognitive processing states. In this study, investigators will use functional near-infrared spectroscopy (fNIRS) to measure oxygenated (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin activation in various parts of the cortex, combined with mood and cognitive scales.

Brain metabolism, measured using 2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) imaging, can guide clinicians in both research and clinical evaluation, with specific patterns of brain metabolism reduction aiding in the diagnosis of AD or related disorders. The PET tracer DPA-714, binding to the 18 kDa translocator protein (TSPO), provides a non-invasive measure of neuroinflammation in activated microglia/macrophages within the mitochondria. The primary objective of this study is to observe differences in brain functional activation, brain metabolism, and brain neuroinflammatory levels between subjects on long-term BZDs use and those not taking BZDs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2026
• Est. primary completion date: February 20, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Continuous use of benzodiazepines for =3 months, matched with participants who have not taken benzodiazepines.

2. Education time =6 years.

3. Abstained from alcohol, coffee, and other psychoactive substances in the 24 hours before the examination.

Exclusion Criteria:

1. Brain damage due to various reasons (such as head trauma, dementia, epilepsy, brain tumors, etc.).

2. Severe systemic diseases (such as malignant tumors, etc.).

3. Acute cerebrovascular disease in the past 3 months. History of substance abuse other than benzodiazepines (such as alcohol, opioids, etc.).

4. Inability to cooperate with fNIRS, PET/MRI examinations, and scale assessments.

Related Conditions & MeSH terms

• Benzodiazepine Dependence
• Depression
• Depression, Anxiety

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Dalian Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain hemodynamic activity with fNIRS	This includes changes in the concentration of oxygenated and deoxygenated hemoglobin as measured by the change in light absorption.	for 2 years
Primary	Longitudinal evolution of biomarkers measured from structural neuroimaging (MRI) and molecular neuroimaging (18F-FDG PET/MRI?DPA-714-PET/MRI)	Estimates of brain TSPO concentrations measured with PET will serve as a marker for neuroinflammation. Variation of the regional cerebral glucose consumption and TSPO-PET measures will be compared between three groups.	for 2 years
Secondary	Mini-Mental State Evaluation (MMSE)	Clinician-administered screening tool used to systematically and thoroughly assess mental status through five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. Scores range between 0-30. A score of 25 or higher is classed as normal. If the score is below 24, the result is usually considered to be abnormal, indicating possible cognitive impairment.	About 15 min during the study visit
Secondary	Scores of Hamilton Depression Scale	Using to assess depressive symptoms. With higher scores associated with more severe depression symptoms. Total scores <7 is normal; Mild depression with total scores of 7~17; Moderate depression with total scores of 18~24; Total scores >24 for severe depression.	About 15 min during the study visit
Secondary	Scores of Hamilton Anxiety Scale	Using to assess anxiety symptoms. With higher scores associated with more severe anxiety symptoms. Total scores< 7 indicates no anxiety; Total scores=7 indicates possible anxiety; Total scores=14 indicates anxiety; Total scores=21 indicates obvious anxiety; Total scores=29 points indicates serious anxiety.	About 15 min during the study visit
Secondary	Pittsburgh Sleep Quality Index	Using to assess the sleep quality. Total scores of 0-5 indicates that the quality of sleep is very good, 6~10 indicates that the quality of sleep is OK, 11~15 indicates that the quality of sleep is average, and 16~21 indicates that the quality of sleep is poor.	About 15 min during the study visit