Major Depressive DisorderPhase 2NCT03430869
Pathophysiology of Neurodegeneration in Late-life Depression (AV45+THK)
A Phase 2 study testing F-18 AV-45 and F-18-THK-5351 in people with Major Depressive Disorder, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
Late-life depression has been frequently associated with cognitive impairment. Several meta-analyses consistently suggested that a history of depression approximately doubles an individual's risk for developing dementia later in life. Neurodegeneration may play an important component in late-life depression. Read more about this study
- Who is it for?
- Ages 50 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- F-18 AV-45 and F-18-THK-5351
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteTaiwan
- Study dates
- 23 Mar 2018to 31 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 50 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Enrolled subjects will be 50 to 90 years of age. They should understand the content of consent and sign consent after the explanation of the benefits and possible side effects of this trial
- Patients with a clinical diagnosis of major depressive disorder according to the DSM -5 criteria (APA, 2013).
- Comparison subjects evaluated for lifetime absence of psychiatric illness by MINI interview (Sheehan et al., 1998).
- Fertile females must avoid becoming pregnant and must use adequate contraceptive methods for 30 days after administration of study radiotracer.
Who cannot join
- Any subject has clinically definite diagnosis of dementia before study recruitment according to the NIA-AA criteria for possible or probable clinically-defined AD dementia ( McKhann, 2011) or the DSM -5 criteria for any type of dementia (APA, 2013).
- Any subject has clinically significant or unstable medical diseases including metabolic, renal, liver, lung or cardiovascular disorders including metabolic, renal, liver, lung or cardiovascular disorders
- Any subject has a current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or epilepsy
- Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or previously prolonged history of substances abuse
- Any females who is pregnant or lactating
- General MRI, and/or PET exclusion criteria including subjects who are pregnant, or had received brain aneurysm surgery, or implanted pacemaker, mechanical valves or cochlear implant.
- Any subjects with history of severe allergic or anaphylactic reactions particularly to the study medication, or any subjects who are recognized as high risk of adverse effects by principle investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploring and Subtyping the Pathophysiology of Neurodegeneration in Late-life Depression: Implications for Treatment and Prognosis in the Future
Late-life depression has been frequently associated with cognitive impairment. Several meta-analyses consistently suggested that a history of depression approximately doubles an individual's risk for developing dementia later in life. Neurodegeneration may play an important component in late-life depression. The pathophysiology behind the link between late-life depression and the subsequent development of dementia largely remains unclear, and should be heterogeneous. This highlights the need to identify specific neurodegenerative pathways involved in late-life depression, which will facilitate research on mechanisms and new treatments in the future.
The recently published the National Institute on Aging and the Alzheimer Association (NIA-AA) criteria might provide new insights and frameworks to explore the patterns of neurodegenerative process in elderly depressed patients and to categorize them into different biomarker-based groups. In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. Alzheimer's disease pathology (A) was determined by measuring Aβ deposition by F-18 AV-45 PET, and neurodegeneration (N) was established by measuring hippocampal volume using MRI. Individuals were categorised as A-N-, A+N-, A+N+, or suspected non-Alzheimer's disease pathophysiology (A-N+, SNAP). All subjects will further undergo F-18-THK-5351 image study to detect underlying tau pathology. By doing this, the investigators will elucidate the neurodegenerative pathophysiology behind the link between depressive disorder and the subsequent development of dementia.
Read the detailed description
Visit 1, Screening assessments (Day 1)
The purpose is to determine eligibility for the proposed study. Screening period may take place over several days to one week after the first visit. Screening assessments will include:
- Study explanations and obtainment of informed consent;
- Inclusion and exclusion Criteria;
- Demographics, medical history, and concomitant medications;
- Clinical characteristic of MDD;
- Safety measurements include vital sign, ECGs and laboratory tests. In addition, a pregnancy test will be performed at screening for females who are of childbearing potential (not for subjects with postmenopause period). A resting ECG and laboratory tests will be taken during the period of the study visit or had been done within 3 months before study visit.
- Fertile females must avoid becoming pregnant 30 days after administration of F-18 AV-45 and 18F-THK-5351.The investigators will advise fertile females to use adequate contraceptive methods during this period, e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream or occlusive cap(diaphragm or cervical/vault caps) with spermicidal foam /gel /film /cream. In addition, a pregnancy test will be performed at screening for females who are of childbearing potential (the test must be negative).This test is not applicable for female subjects with postmenopausal period; permanently sterilized (eg, bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy.
- Cognitive function assessment includes MMSE, CDR and comprehensive neurocognitive battery.
Visit 2, Image study (Month 1±14 days) F-18 AV-45 PET study will be conducted for all subjects. PET data will be acquired using SIMENS PET/CT or PET/MRI scanner. For PET/CT protocol, a dynamic brain PET scan will be started simultaneously with the injection of F-18 AV-45 PET after a low-dose CT scan for patient positioning and attenuation correction. Instead of PET/CT, the investigators will also consider PET/MRI for better soft tissue contrast and limited radiation exposure for multiple scan session. However, the attenuation map delineated from MRI is not consistent, and the delicate PET/MRI protocol is still under evaluation. Vital sign will be checked before and at the end of the image study for all subjects. Subjects will be continuously observed for signs of adverse events or serious adverse events. Each study participant (or their caregiver if applicable) will be contacted by phone approximately 7-14 days after the PET imaging study or at the next follow-up visit of outpatient department to confirm their well-being and query them about any new adverse events. Study-emergent AEs will be monitored till resolution or relatively stable state.
Visit 3, Image study (Month 1±14 days) All participants will receive F-18-THK-5351 PET image study. PET data will be acquired using SIMENS PET/CT or PET/MRI scanner. For PET/CT protocol, a dynamic brain PET scan will be started simultaneously with the injection of F-18-THK-5351 after a low-dose CT scan for patient positioning and attenuation correction. Instead of PET/CT, the investigators will also consider PET/MRI for better soft tissue contrast and limited radiation exposure for multiple scan session. However, the attenuation map delineated from MRI is not consistent, and the delicate PET/MRI protocol is still under evaluation. Vital sign will be checked before and after the image study. Safety measurements include ECG, and clinical labs will be performed at the end of the image study for all subjects. Subjects will be continuously observed for signs of adverse events or serious adverse events. Each study participant (or their caregiver if applicable) will be contacted by phone approximately 7-14 days after the PET imaging study or at the next follow-up visit of outpatient department to confirm their well-being and query them about any new adverse events. Study-emergent AEs will be monitored till resolution or relatively stable state.
- Conditions
- Major Depressive Disorder
- Being tested
- F-18 AV-45, F-18-THK-5351
- Keywords
- late-life depression, major depressive disorder, Alzheimer's disease dementia, neurodegeneration, amyloid plague, tau protein
- Medical subject headings
- Depressive Disorder, Major, Nerve Degeneration, Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
F-18 AV-45Drug
In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. Alzheimer's disease pathology (A) was determined by measuring Aβ deposition by F-18 AV-45 PET.
F-18-THK-5351Drug
In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. All subjects will further undergo F-18-THK-5351 image study to detect underlying tau pathology. By doing this, the investigators will elucidate the neurodegenerative pathophysiology behind the link between depressive disorder and the subsequent development of dementia.
| Study group | Role | What they receive |
|---|---|---|
| F-18 AV-45 | Experimental | F-18 AV-45 imaging Receives: Drug: F-18 AV-45 |
| F-18-THK-5351 | Experimental | F-18-THK-5351 imaging Receives: Drug: F-18-THK-5351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The standard uptake value ratio (SUVR) of 18F-florbetapir
The primary outcome is to measure the standard uptake value ratio (SUVR) of 18F-florbetapir in patients with major depressive disorder and compare the difference between patients and non-depressed subjects. 18F-florbetapir SUVRs of each volume of interest are analyzed using whole the cerebellum as the reference region.
Measured: three years
Secondary outcomes (1)
The standard uptake value ratio (SUVR) of 18F-THK-5351
The secondary outcome is to measure the standard uptake value ratio (SUVR) of 18F-THK-5351 in patients with major depressive disorder and compare the difference between patients and non-depressed subjects. 18F-THK-5351 SUVRs of each volume of interest are analyzed using the pons as the reference region.
Measured: three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2018
- Study start23 Mar 2018
- Primary completion28 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- KUAN YI WU, Principal investigator, Attending physician
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03430869
- Sponsor's protocol ID
- 201601655A0
- Status last verified
- Jul 2021
- First submitted
- 20 Nov 2017
- Last updated
- 26 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring and Subtyping the Pathophysiology of Neurodegeneration in Late-life Depression: Implications for Treatment and Prognosis in the Future
- ClinicalTrials.gov ID
- NCT03430869
- Acronym / sponsor ID
- 201601655A0
- Conditions
- Major Depressive Disorder
- Keywords
- late-life depression, major depressive disorder, Alzheimer's disease dementia, neurodegeneration, amyloid plague, tau protein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 23 Mar 2018 (actual)
- Primary completion
- 28 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 13 Feb 2018 (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.
Late-life depression has been frequently associated with cognitive impairment. Several meta-analyses consistently suggested that a history of depression approximately doubles an individual's risk for developing dementia later in life. Neurodegeneration may play an important component in late-life depression. The pathophysiology behind the link between late-life depression and the subsequent development of dementia largely remains unclear, and should be heterogeneous. This highlights the need to identify specific neurodegenerative pathways involved in late-life depression, which will facilitate research on mechanisms and new treatments in the future.
The recently published the National Institute on Aging and the Alzheimer Association (NIA-AA) criteria might provide new insights and frameworks to explore the patterns of neurodegenerative process in elderly depressed patients and to categorize them into different biomarker-based groups. In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. Alzheimer's disease pathology (A) was determined by measuring Aβ deposition by F-18 AV-45 PET, and neurodegeneration (N) was established by measuring hippocampal volume using MRI. Individuals were categorised as A-N-, A+N-, A+N+, or suspected non-Alzheimer's disease pathophysiology (A-N+, SNAP). All subjects will further undergo F-18-THK-5351 image study to detect underlying tau pathology. By doing this, the investigators will elucidate the neurodegenerative pathophysiology behind the link between depressive disorder and the subsequent development of dementia.
Detailed description
Visit 1, Screening assessments (Day 1)
The purpose is to determine eligibility for the proposed study. Screening period may take place over several days to one week after the first visit. Screening assessments will include:
- Study explanations and obtainment of informed consent;
- Inclusion and exclusion Criteria;
- Demographics, medical history, and concomitant medications;
- Clinical characteristic of MDD;
- Safety measurements include vital sign, ECGs and laboratory tests. In addition, a pregnancy test will be performed at screening for females who are of childbearing potential (not for subjects with postmenopause period). A resting ECG and laboratory tests will be taken during the period of the study visit or had been done within 3 months before study visit.
- Fertile females must avoid becoming pregnant 30 days after administration of F-18 AV-45 and 18F-THK-5351.The investigators will advise fertile females to use adequate contraceptive methods during this period, e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream or occlusive cap(diaphragm or cervical/vault caps) with spermicidal foam /gel /film /cream. In addition, a pregnancy test will be performed at screening for females who are of childbearing potential (the test must be negative).This test is not applicable for female subjects with postmenopausal period; permanently sterilized (eg, bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy.
- Cognitive function assessment includes MMSE, CDR and comprehensive neurocognitive battery.
Visit 2, Image study (Month 1±14 days) F-18 AV-45 PET study will be conducted for all subjects. PET data will be acquired using SIMENS PET/CT or PET/MRI scanner. For PET/CT protocol, a dynamic brain PET scan will be started simultaneously with the injection of F-18 AV-45 PET after a low-dose CT scan for patient positioning and attenuation correction. Instead of PET/CT, the investigators will also consider PET/MRI for better soft tissue contrast and limited radiation exposure for multiple scan session. However, the attenuation map delineated from MRI is not consistent, and the delicate PET/MRI protocol is still under evaluation. Vital sign will be checked before and at the end of the image study for all subjects. Subjects will be continuously observed for signs of adverse events or serious adverse events. Each study participant (or their caregiver if applicable) will be contacted by phone approximately 7-14 days after the PET imaging study or at the next follow-up visit of outpatient department to confirm their well-being and query them about any new adverse events. Study-emergent AEs will be monitored till resolution or relatively stable state.
Visit 3, Image study (Month 1±14 days) All participants will receive F-18-THK-5351 PET image study. PET data will be acquired using SIMENS PET/CT or PET/MRI scanner. For PET/CT protocol, a dynamic brain PET scan will be started simultaneously with the injection of F-18-THK-5351 after a low-dose CT scan for patient positioning and attenuation correction. Instead of PET/CT, the investigators will also consider PET/MRI for better soft tissue contrast and limited radiation exposure for multiple scan session. However, the attenuation map delineated from MRI is not consistent, and the delicate PET/MRI protocol is still under evaluation. Vital sign will be checked before and after the image study. Safety measurements include ECG, and clinical labs will be performed at the end of the image study for all subjects. Subjects will be continuously observed for signs of adverse events or serious adverse events. Each study participant (or their caregiver if applicable) will be contacted by phone approximately 7-14 days after the PET imaging study or at the next follow-up visit of outpatient department to confirm their well-being and query them about any new adverse events. Study-emergent AEs will be monitored till resolution or relatively stable state.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| F-18 AV-45 | Experimental | Drug: F-18 AV-45F-18 AV-45 imaging |
| F-18-THK-5351 | Experimental | Drug: F-18-THK-5351F-18-THK-5351 imaging |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Enrolled subjects will be 50 to 90 years of age. They should understand the content of consent and sign consent after the explanation of the benefits and possible side effects of this trial
- Patients with a clinical diagnosis of major depressive disorder according to the DSM -5 criteria (APA, 2013).
- Comparison subjects evaluated for lifetime absence of psychiatric illness by MINI interview (Sheehan et al., 1998).
- Fertile females must avoid becoming pregnant and must use adequate contraceptive methods for 30 days after administration of study radiotracer.
Key exclusion criteria (7 listed)
- Any subject has clinically definite diagnosis of dementia before study recruitment according to the NIA-AA criteria for possible or probable clinically-defined AD dementia ( McKhann, 2011) or the DSM -5 criteria for any type of dementia (APA, 2013).
- Any subject has clinically significant or unstable medical diseases including metabolic, renal, liver, lung or cardiovascular disorders including metabolic, renal, liver, lung or cardiovascular disorders
- Any subject has a current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or epilepsy
- Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or previously prolonged history of substances abuse
- Any females who is pregnant or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| F-18 AV-45In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. Alzheimer's disease pathology (A) was determined by measuring Aβ deposition by F-18 AV-45 PET. | Drug | F-18 AV-45 |
| F-18-THK-5351In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. All subjects will further undergo F-18-THK-5351 image study to detect underlying tau pathology. By doing this, the investigators will elucidate the neurodegenerative pathophysiology behind the link between depressive disorder and the subsequent development of dementia. | Drug | F-18-THK-5351 |
Primary outcome
The standard uptake value ratio (SUVR) of 18F-florbetapir
Time frame: three years
The primary outcome is to measure the standard uptake value ratio (SUVR) of 18F-florbetapir in patients with major depressive disorder and compare the difference between patients and non-depressed subjects. 18F-florbetapir SUVRs of each volume of interest are analyzed using whole the cerebellum as the reference region.
1 secondary outcome
The standard uptake value ratio (SUVR) of 18F-THK-5351
Time frame: three years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2022.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
KUAN YI WU principal investigator
Attending physician
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing F-18 AV-45 and F-18-THK-5351 in people with Major Depressive Disorder, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
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 4 inclusion and 7 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: finished, as of the sponsor's last update on 26 Jan 2022. 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 Taiwan. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The standard uptake value ratio (SUVR) of 18F-florbetapir (time frame: three years). 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 26 Jan 2022.