Clinical trial NCT06250842: Benzodiazepine Impact on Cognitive Function: fNIRs and PET/MRI Study
Official title: Assessing the Cognitive Effects of Chronic Benzodiazepine Use in Patients: A Comprehensive Study Using fNIRs and PET/MRI Technologies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Benzodiazepine Adverse Reaction
Depression, Anxiety
Benzodiazepine Dependence
Keywords: Benzodiazepines
Long Term Adverse Effects
Cognitive Neuroscience
Neuroendocrinology
immunomodulatory potential
Lead sponsor: The First Affiliated Hospital of Dalian Medical University
Sponsor class: OTHER
First posted: 2024-02-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
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: The First Affiliated Hospital of Dalian Medical University

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Brain hemodynamic activity with fNIRS
timeFrame: for 3 years
measure: Longitudinal evolution of biomarkers measured from neuroimaging (including structural, functional, and multimodal MRI) and molecular neuroimaging (18F-FDG PET/MRI、DPA-714-PET/MRI)
timeFrame: for 3 years
Secondary outcomes:
measure: Mini-Mental State Evaluation (MMSE)
timeFrame: About 15 min during the study visit
measure: Scores of Hamilton Depression Scale
timeFrame: About 15 min during the study visit
measure: Scores of Hamilton Anxiety Scale
timeFrame: About 15 min during the study visit
measure: Pittsburgh Sleep Quality Index
timeFrame: About 15 min during the study visit
Other outcomes:
Locations:
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
Study officials:
affiliation: The First Affiliated Hospital of Dalian Medical University
name: Hui min Zhang
role: PRINCIPAL_INVESTIGATOR
References: