Major Depressive Disorder Clinical Trial
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.
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: 1. Study explanations and obtainment of informed consent; 2. Inclusion and exclusion Criteria; 3. Demographics, medical history, and concomitant medications; 4. Clinical characteristic of MDD; 5. 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. 6. 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. 7. 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. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05537558 -
Precision Medicine for the Prediction of Treatment (PROMPT) Response (PROMPT)
|
||
Terminated |
NCT02192099 -
Open Label Extension for GLYX13-C-202, NCT01684163
|
Phase 2 | |
Completed |
NCT03142919 -
Lipopolysaccharide (LPS) Challenge in Depression
|
Phase 2 | |
Recruiting |
NCT05547035 -
Identification of Physiological Data by a Wearable Monitor in Subjects Suffering From Major Depression Disorders
|
N/A | |
Terminated |
NCT02940769 -
Neurobiological Effects of Light on MDD
|
N/A | |
Recruiting |
NCT05892744 -
Establishing Multimodal Brain Biomarkers for Treatment Selection in Depression
|
Phase 4 | |
Recruiting |
NCT05537584 -
SMART Trial to Predict Anhedonia Response to Antidepressant Treatment
|
Phase 4 | |
Active, not recruiting |
NCT05061706 -
Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
|
Phase 3 | |
Completed |
NCT04479852 -
A Study of the Safety and Efficacy of SP-624 in the Treatment of Adults With Major Depressive Disorder
|
Phase 2 | |
Recruiting |
NCT04032301 -
Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans
|
Phase 1 | |
Recruiting |
NCT05527951 -
Enhanced Measurement-Based Care Effectiveness for Depression (EMBED) Study
|
N/A | |
Completed |
NCT03511599 -
Cycloserine rTMS Plasticity Augmentation in Depression
|
Phase 1 | |
Recruiting |
NCT04392947 -
Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
|
N/A | |
Recruiting |
NCT05895747 -
5-HTP and Creatine for Depression R33 Phase
|
Phase 2 | |
Recruiting |
NCT05273996 -
Predictors of Cognitive Outcomes in Geriatric Depression
|
Phase 4 | |
Recruiting |
NCT05813093 -
Interleaved TMS-fMRI in Ultra-treatment Resistant Depression
|
N/A | |
Recruiting |
NCT05135897 -
The Neurobiological Fundaments of Depression and Its Relief Through Neurostimulation Treatments
|
||
Enrolling by invitation |
NCT04509102 -
Psychostimulant Augmentation of Repetitive TMS for the Treatment of Major Depressive Disorder
|
Early Phase 1 | |
Recruiting |
NCT06026917 -
Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain With Toludesvenlafaxine Hydrochloride Extended-Release Tablets Using 11C-CFT Positron Emission Tomography (PET)
|
Phase 4 | |
Recruiting |
NCT06145594 -
EMA-Guided Maintenance TMS for Depression
|
N/A |