Benzodiazepine Adverse ReactionNCT06250842
Benzodiazepine Impact on Cognitive Function: fNIRs and PET/MRI Study
An observational study of Benzodiazepine Adverse Reaction and Depression, Anxiety, run by The First Affiliated Hospital of Dalian Medical University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Benzodiazepine Adverse Reaction, Depression, Anxiety, Benzodiazepine Dependence
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 11 Feb 2024to 30 Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The First Affiliated Hospital of Dalian Medical University
Who may be able to join
- Continuous use of benzodiazepines for ≥3 months, matched with participants who have not taken benzodiazepines.
- Education time ≥6 years.
- Abstained from alcohol, coffee, and other psychoactive substances in the 24 hours before the examination.
Who cannot join
- Brain damage due to various reasons (such as head trauma, dementia, epilepsy, brain tumors, etc.).
- Severe systemic diseases (such as malignant tumors, etc.).
- Acute cerebrovascular disease in the past 3 months. History of substance abuse other than benzodiazepines (such as alcohol, opioids, etc.).
- Inability to cooperate with fNIRS, PET/MRI examinations, and scale assessments.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Dalian Medical University
Dalian, Liaoning, 116000
Hui min Zhang, +86 18098876233, huiminzhangxs@163.com
Mei chen Liu, +86 18098871637, meichenliu9019@163.com
About this study
Official title: Assessing the Cognitive Effects of Chronic Benzodiazepine Use in Patients: A Comprehensive Study Using fNIRs and PET/MRI Technologies
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.
Read the 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.
- Keywords
- Benzodiazepines, Long Term Adverse Effects, Cognitive Neuroscience, Neuroendocrinology, immunomodulatory potential
- Medical subject headings
- Depression, Anxiety Disorders, Long Term Adverse Effects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Long-term benzodiazepine use group | Continuous use of benzodiazepines for ≥3 months | |
| Non-benzodiazepine use group | No history of prior benzodiazepine use | |
| Healthy Controls | Healthy Controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain hemodynamic activity with fNIRS
This includes changes in the concentration of oxygenated and deoxygenated hemoglobin as measured by the change in light absorption, along with comprehensive analyses of activation values and functional connectivity.
Measured: for 3 years
Longitudinal evolution of biomarkers measured from neuroimaging (including structural, functional, and multimodal 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, derived from neuroimaging (including structural, functional, and multimodal MRI), will be compared between three groups.
Measured: for 3 years
Secondary outcomes (4)
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.
Measured: About 15 min during the study visit
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.
Measured: About 15 min during the study visit
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.
Measured: About 15 min during the study visit
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.
Measured: About 15 min during the study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2024
- Study start11 Feb 2024
- Primary completion20 Feb 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Benzodiazepine Adverse ReactionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital of Dalian Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hui min Zhang, Principal investigator, The First Affiliated Hospital of Dalian Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06250842
- Sponsor's protocol ID
- PJ-KS-KY-2023-577
- Status last verified
- Feb 2025
- First submitted
- 26 Jan 2024
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Cognitive Effects of Chronic Benzodiazepine Use in Patients: A Comprehensive Study Using fNIRs and PET/MRI Technologies
- ClinicalTrials.gov ID
- NCT06250842
- Acronym / sponsor ID
- PJ-KS-KY-2023-577
- Keywords
- Benzodiazepines, Long Term Adverse Effects, Cognitive Neuroscience, Neuroendocrinology, immunomodulatory potential
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Dalian Medical UniversityUniversity, hospital or other
- Study start
- 11 Feb 2024 (actual)
- Primary completion
- 20 Feb 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 9 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Long-term benzodiazepine use group | – | –Continuous use of benzodiazepines for ≥3 months |
| Non-benzodiazepine use group | – | –No history of prior benzodiazepine use |
| Healthy Controls | – | –Healthy Controls |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The First Affiliated Hospital of Dalian Medical University
Key inclusion criteria (3 listed)
- Continuous use of benzodiazepines for ≥3 months, matched with participants who have not taken benzodiazepines.
- Education time ≥6 years.
- Abstained from alcohol, coffee, and other psychoactive substances in the 24 hours before the examination.
Key exclusion criteria (4 listed)
- Brain damage due to various reasons (such as head trauma, dementia, epilepsy, brain tumors, etc.).
- Severe systemic diseases (such as malignant tumors, etc.).
- Acute cerebrovascular disease in the past 3 months. History of substance abuse other than benzodiazepines (such as alcohol, opioids, etc.).
- Inability to cooperate with fNIRS, PET/MRI examinations, and scale assessments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Brain hemodynamic activity with fNIRS
Time frame: for 3 years
This includes changes in the concentration of oxygenated and deoxygenated hemoglobin as measured by the change in light absorption, along with comprehensive analyses of activation values and functional connectivity.
Longitudinal evolution of biomarkers measured from neuroimaging (including structural, functional, and multimodal MRI) and molecular neuroimaging (18F-FDG PET/MRI、DPA-714-PET/MRI)
Time frame: for 3 years
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, derived from neuroimaging (including structural, functional, and multimodal MRI), will be compared between three groups.
4 secondary outcomes
Mini-Mental State Evaluation (MMSE)
Time frame: About 15 min during the study visit
Scores of Hamilton Depression Scale
Time frame: About 15 min during the study visit
Scores of Hamilton Anxiety Scale
Time frame: About 15 min during the study visit
Pittsburgh Sleep Quality Index
Time frame: About 15 min during the study visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hui min Zhang principal investigator
The First Affiliated Hospital of Dalian Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Benzodiazepine Adverse Reaction and Depression, Anxiety, run by The First Affiliated Hospital of Dalian Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hui min Zhang (+86 18098876233, huiminzhangxs@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain hemodynamic activity with fNIRS (time frame: for 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.