Exploration of the Potential Mechanisms of n-3 Fatty Acids Supplementation in Depression and Cognitive Function in Patients With Late-life Depression

Late Life Depression Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05972798
• Other study ID #: 201701653B0
• Status: Completed
• Phase: N/A
• Start date: September 25, 2018
• Est. completion date: December 25, 2020

Study information

• Verified date: January 2018
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 25, 2020
• Est. primary completion date: September 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Late Life Depression

Intervention

Other:
• Omega-3 fatty acids
2.2 g/d omega-3 PUFAs (1.2g EPA and 1g DHA per day) in patients with LLD
• Soybean oil
Soybean oil in patients with LLD

Locations

Country	Name	City	State
Taiwan	Che-min Lin	Keelung

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Loneliness UCLA	the severity of loneliness (the score range from 20-80,the lower score means worse)	Change from Baseline at 52 weeks
Primary	Ham D-17	the insight(the score range from 0-2,the higher score means worse)	Change from Baseline at 52 weeks
Primary	Geriatric Depression Geriatric Depression Scale-15	the insight(the score range from 0-1,the higher score means worse)	Change from Baseline at 52 weeks
Secondary	Pittsburgh Sleep Quality Index (PSQI)	Sleep related scales	Change from Baseline at 52 weeks
Secondary	Hamilton Rating Scale for Anxiety (HAM-A)	the insight(the score range from 0-56,the higher score means worse)	Change from Baseline at 52 weeks
Secondary	Verbal Learning & Memory	Word list of Wechsler Memory Scale-III Face memory task(the score range from 0-48,the higher score means better)	Change from Baseline at 52 weeks
Secondary	structural and functional connectivity	Brain MRI connectivity change	Change from Baseline at 52 weeks
Secondary	Mini-Mental State Examination (MMSE)	The test consists of questions that assess orientation to place and time, learning and memory, construction ability, attention, and calculation skill.	Change from Baseline at 52 weeks
Secondary	Total Brain-derived neurotrophic factor	Total BDNF	Change from Baseline at 52 weeks
Secondary	Free Brain-derived neurotrophic factor	Free BDNF	Change from Baseline at 52 weeks
Secondary	Interleukin-6	IL-6	Change from Baseline at 52 weeks
Secondary	Interleukin-1ß	IL-1ß	Change from Baseline at 52 weeks
Secondary	Interleukin-12	IL-12	Change from Baseline at 52 weeks