Clinical trial NCT05972798: Exploration of the Potential Mechanisms of n-3 Fatty Acids Supplementation in Depression and Cognitive Function in Patients With Late-life Depression
Official title: Exploration of the Potential Mechanisms of n-3 Fatty Acids Supplementation in Depression and Cognitive Function in Patients With Late-life Depression by Using Multi-modal Neuroimaging Methods
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Late Life Depression
Keywords: elderly depression
long-chain polyunsaturated omega-3 fatty acids
cognitive function
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2023-08-02
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Depression in the elderly causes considerable distress, disability, and loss of life. The accelerating aging boom is accentuating the importance of addressing late life depression (LLD). Extensive efforts in searching for effective and safety treatment yielded unsatisfactory results. Among the multiple agents in LLD treatment, long-chain polyunsaturated omega-3 fatty acids (omega-3 PUFA) stands out as an interesting compound as it addressed two main features in LLD, depressive mood and cognitive function. However, how it affects the brain remains unknown. Therefore, in an on-going double-blind randomized placebo-controlled study using 48 weeks omega-3 PUFA supplement in LLD treatment, we plan to perform two MRI scans (pre-treatment and post-treatment), in an effort to understand the unique neurobiology of omega-3 PUFA in the treatment of LLD. Along the trial, neuropsychological function and associated inflammatory markers were also collected.

Detailed description: Depression in the elderly causes considerable distress, disability, and loss of life. The accelerating aging boom is accentuating the importance of addressing late life depression (LLD).Extensive efforts in searching for effective and safety treatment yielded unsatisfactory results.Among the multiple agents in LLD treatment, long-chain polyunsaturated omega-3 fatty acids(omega-3 PUFA) stands out as an interesting compound as it addressed two main features in LLD,depressive mood and cognitive function. However, how it affects the brain remains unknown.Therefore, in an on-going double-blind randomized placebo-controlled study using 48 weeks omega-3 PUFA supplement in LLD treatment, we plan to perform two MRI scans (pre-treatment and post-treatment), in an effort to understand the unique neurobiology of omega-3 PUFA in the treatment of LLD. Along the trial, neuropsychological function and associated inflammatory markers were also collected.

From past study, what separates LLD from mid-life depression lying in two key features that distinguish the brain in the elderly versus young individuals are cerebrovascular disease (CVD) and neurodegeneration. We conceptualize the cognitive and emotional dysfunction in LLD is obscured by the overlay of age-related brain abnormalities (e.g., white matter disease, atrophy, neurodegeneration, etc.), which could be ameliorated by the supplement omega-3 PUFA. We also expected functionally distinct brain regions (ex: amygdala in emotional processing, hippocampus in memory encoding) will demonstrate between group differences in the activation changes across trial. Moreover, all these neuroimaging changes may be mediated by concomitant changes in inflammatory markers or neuropsychological profiles, validating the mechanism of action in omega-3 PUFA as anti-inflammation.

With the help with multi-modal neuroimaging approach, we can assimilate these findings into an 'integrative neurobiological systems". We expect our findings would pin-point omega-3 PUFA's antidepressant effect in the brain level and solve its underlying biological mechanism.

Eligibility criteria: Inclusion Criteria:

1. Age \> 60 years.
2. Previous major depressive disorder (MDD), single or recurrent.
3. Mood is relatively stable for at least 3 weeks and the score of 17-item Hamilton Depression Rating Scale (HAMD-17) less than 10

Exclusion Criteria:

1. Inability to provide informed consent.
2. Depressive symptoms severe enough (i.e., HAMD-17 \>= 10) at the baseline.
3. Dementia, as defined by MMSE \< 24 and clinical evidence of dementia.
4. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
5. Abuse of or dependence on alcohol or other substances within the past 3 months, and confirmed by study physician interview.
6. High risk for suicide (e.g., active SI and/or current/recent intent or plan) AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.
7. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
8. Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician and study physician's clinical judgment.

Primary outcomes:
measure: Loneliness UCLA
timeFrame: Change from Baseline at 52 weeks
measure: Ham D-17
timeFrame: Change from Baseline at 52 weeks
measure: Geriatric Depression Geriatric Depression Scale-15
timeFrame: Change from Baseline at 52 weeks
Secondary outcomes:
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Change from Baseline at 52 weeks
measure: Hamilton Rating Scale for Anxiety (HAM-A)
timeFrame: Change from Baseline at 52 weeks
measure: Verbal Learning & Memory
timeFrame: Change from Baseline at 52 weeks
measure: structural and functional connectivity
timeFrame: Change from Baseline at 52 weeks
measure: Mini-Mental State Examination (MMSE)
timeFrame: Change from Baseline at 52 weeks
measure: Total Brain-derived neurotrophic factor
timeFrame: Change from Baseline at 52 weeks
measure: Free Brain-derived neurotrophic factor
timeFrame: Change from Baseline at 52 weeks
measure: Interleukin-6
timeFrame: Change from Baseline at 52 weeks
measure: Interleukin-1β
timeFrame: Change from Baseline at 52 weeks
measure: Interleukin-12
timeFrame: Change from Baseline at 52 weeks
Other outcomes:
Locations:
city: Keelung
country: Taiwan
facility: Che-min Lin
Study officials:
References: