Alzheimer DiseaseNCT04972643
The Protective Effect of Omega-3 Fatty Acid on Cognitive Function Among Patients With Mild Dementia
A study testing EPA and DHA in people with Alzheimer Disease and Dementia Disorder, run by Taichung Veterans General Hospital at 1 site in Taiwan.
Trial summary
Background： Dementia is a progressive, devastating, and fatal neurodegenerative disorder. Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 50% of patients with dementia. Read more about this study
- Who is it for?
- Ages 65 to 105 years
- Conditions the study is for
- Alzheimer Disease, Dementia Disorder
- What is being tested?
- EPA and DHA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 163 participants
- Where
- 1 siteTaiwan
- Study dates
- 23 Sep 2012to 23 Sep 2018
- Phase
- Interventional
- 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 65 to 105 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients may be included in the study if they meet the following criteria:
- Males and females over 65 years of age.
- Diagnosis of Alzheimer's Dementia disorder.
- Each individual must have a level of understanding sufficient to perform all tests and examinations required.
- Individuals must be willing to accept all laboratory examinations and MRI examination.
- Individuals must be willing to provide a small sample of blood for evaluation.
- Individuals must be willing to participate in a short 30-60 minute clinical interview.
Who cannot join
- Patients may be excluded from the study for any of the following reasons:
- Serious unstable illness such that death is anticipated within 1 year or intensive care unit hospitalization for the condition is anticipated within 6 months.
- Diagnosis of Vascular Dementia disorder.
- Uncorrected hypothyroidism or hyperthyroidism
- Participants will be excluded if they had evidence of epilepsy; focal brain lesion; head injury with loss of consciousness or confusion after the injury; DSMIV-TR (text revision) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, or alcohol or substance abuse; or potential bleeding tendency.
- History of allergy to fish or omega-3 polyunsaturated fatty acids.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Taichung Veterans General Hospital
Taichung, No.450,Sec.1,Dongda Rd.,Xitun Dist., 40764
About this study
Official title: Department of Psychiatry, Taichung Veterans General Hospital
Background： Dementia is a progressive, devastating, and fatal neurodegenerative disorder. Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 50% of patients with dementia. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the major bioactive components of n-3 polyunsaturated fatty acids (n-3 PUFAs) , might connect to the etiology of several neuropsychiatric diseases. To our knowledge, it has never been studied to look at the different effects of DHA, EPA and their combination on associated symptoms of AD.
Objectives To examine the effects of DHA, EPA and their combination on associated symptoms of AD, including cognitive function, depressive symptoms, and functional ability.
Method This is a randomized, double-blind, placebo-controlled, 24-month follow-up study, enrolling 200-400 patients with mild AD (Mini-Mental Status Examination (MMSE) 19-26 or Clinical Dementia Rating (CDR) 0.5-1). Cognitive ability is assessed by the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the MMSE. Mood status is assessed by Geriatric Depression Scale (GDS). Functional ability is assessed by the Alzheimer Disease Cooperative Study activities of daily living (ADCS-ADL) and global function by the CDR, quality of life scale (QOL-AD). Brain function is assessed by resting state brain magnetic resonance imaging (MRI).
Read the detailed description
Background Dementia is a progressive, devastating, and fatal neurodegenerative disorder (Cummings, 2004). As of 2010, there are an estimated 35.6 million people with dementia worldwide. By 2050, it is projected that this figure will have increased to over 115 million (1, 2). Therefore, dementia is not only an important medical disease but also a public health issue to demand immediate attention. A conservative estimate of economic burden from dementia (based on Alzheimer's Society's Dementia United Kindom (UK) report published in February 2007) reaches 20 billion by the year 2010, which suggests an average cost of 25,472 per person annually. It indicated a heavy social financial expense for the whole world in general. Alzheimer's disease (AD) is the most common cause of dementia, accounting for 60-80% of patients with dementia. Given that it is still lacking in effective treatments for AD, there has been growing interest in early detection and prevention for this disastrous illness. Delaying AD onset by 1 year could potentially lower its incidence by more than 9 million cases over the next 40 years (3).
Dementia could be resulted from numerous risk factors and medical conditions including vascular risk factors (e.g. hypertension, diabetes, and obesity), psychosocial factors (e.g. depression), and health behaviors (e.g. physical inactivity and smoking) (4, 5). Indeed, reflecting its heterogeneity, several hypotheses have been proposed for etiology of dementia, including genetic susceptibility, vascular changes, inflammatory process, oxidative stress, and recently, n-3 polyunsaturated fatty acids (n-3 PUFAs) (Fratiglioni et al., 2008;Samieri et al., 2008;Cole and Frautschy, 2010;Mucke and Pitas, 2004;Gomez-Pinilla, 2008). PUFAs are classified into mainly n-3 (or omega-3) and n-6 (or omega-6) groups. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the major bioactive components of n-3 PUFAs, are associated with neuronal membrane stability and fluidity, neurogenesis, neuroplasticity, neurotransmission and anti-inflammation, which might connect to the etiology of several neuropsychiatric diseases including depression and dementia (Horrobin and Bennett, 1999;Su et al., 2000;Chalon, 2006;Lukiw and Bazan, 2006;Su, 2009b;Lin et al., 2010a). On the other hand, arachidonic acid (AA), the major components of n-6 PUFAs, is a precursor of eicosanoids and is important to modulate proinflammatory effects, which might also link to the pathogenesis of neuroinflammatory and neurodegenerative diseases like dementia (Sanchez-Mejia and Mucke, 2010;Lukiw and Bazan, 2010). Consistent with the theoretical relevance, evidences to link PUFAs to dementia have been reported extensively from more epidemiological studies. For example, it has been observed that regions with a high consumption of fish, which are good sources of n-3 PUFAs, appear to have a lower prevalence of dementia (Barberger-Gateau et al., 2002;Barberger-Gateau et al., 2007;Huang et al., 2005;Morris et al., 2003;Kalmijn et al., 1997) and Mild cognitive Impairment (MCI) ;(Roberts et al., 2010)). Although clinical studies until now have failed to demonstrate beneficial effects of n-3 PUFA supplementation in patients with moderate or severe AD (Freund-Levi et al., 2006a;Quinn et al., 2010a), it may benefit in patients with mild AD or MCI and those without apolipoprotein E(APOE) ε4 allele (Freund-Levi et al., 2006b;Chiu et al., 2008;Quinn et al., 2010b). In addition, the two main n-3 PUFAs have different biological effects. DHA is the main n-3 PUFAs in the brain and is important in neuroplasticity and neuroprotection. EPA, on the other hand, is very little in the brain but is important in modulate inflammation and immune function (Lin et al., 2010b;Su, 2009a). To our knowledge, it has never been studied to look at the different effects of DHA, EPA and their combination on different associated symptoms of AD. To provide more evidence for the association between n-3 PUFAs and associated symptoms of AD, including cognitive function, depression, and physical activity in AD, we propose to conduct this double-blind, placebo-controlled, 24-month research. In addition, neuroprotective effects of vitamin B, preliminary findings in recent studies have shown cognitive-protection effects of it among patients with MCI. Moreover, deficiency of vitamin B is known to cause nervousness, depression, and peripheral and central neuropathy. The importance of vitamin B in developmental processes of the brain is supported by the findings that vitamin B deficiency at certain stages of brain development interferes with brain cell proliferation, migration and maturation . Vitamin B affords survival-promoting activities on cultured brain neurons (6). This is probably the first study to evaluate the effects of vitamin B on cognitive protection among Asian patients with AD. Based on the review of the possible benefits from n-3 PUFAs supplement on cognitive function preservation after balancing for its slightest side effects, we here propose a randomized clinical trial study design to test whether Hypothesis Omega-3 PUFAs is protective against cognitive decline among people with mild AD.
Primary Aim To examine whether consumption of n-3 PUFAs protects against cognitive decline in patients with mild AD.
Secondary Aims
- To examine the different effects of DHA, EPA and their combination on different symptoms of AD.
- To examine whether consumption of n-3 PUFAs improves cognitive function in patients with mild AD.
- To examine whether consumption of n-3 PUFAs improves depressive symptoms in patients with mild AD.
- To examine whether consumption of n-3 PUFAs improves physical activity level in patients with mild AD.
Significance of Study
- To provide a simple way through dietary supplement of n-3 PUFAs to prevent cognitive decline and improve depressive symptoms and physical activity in patients with mild AD.
- No placebo-controlled studies regarding n-3 PUFAs in cognitive prevention have been conducted among Asian people.
- Conditions
- Alzheimer Disease, Dementia Disorder
- Being tested
- EPA, DHA, Placebo
- Keywords
- Dementia Alzheimer
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EPADietary supplement
EPA 2000mg Soft capsules
DHADietary supplement
DHA 2000mg Soft capsules
PlaceboDietary supplement
Placebo Soft capsules
| Study group | Role | What they receive |
|---|---|---|
| EPA and DHA intervention | Experimental | EPA 1000mg and DHA 1000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. Receives: Dietary Supplement: EPA; Dietary Supplement: DHA |
| EPA intervention | Experimental | EPA 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. Receives: Dietary Supplement: EPA |
| DHA intervention | Experimental | DHA 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. Receives: Dietary Supplement: DHA |
| Placebo | Placebo comparator | Placebo 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aspartate Aminotransferase (AST)
Measured: Day 0
Aspartate Aminotransferase (AST)
Measured: Day 24 month
Alanine Aminotransferase (ALT)
Measured: Day 0
Alanine Aminotransferase (ALT)
Measured: Day 24 month
Albumin level
Measured: Day 0
Albumin level
Measured: Day 24 month
Fasting blood glucose
Measured: Day 0
Fasting blood glucose
Measured: Day 24 month
Blood Urea Nitrogen (BUN)
Measured: Day 0
Blood Urea Nitrogen (BUN)
Measured: Day 24 month
Creatinine level
Measured: Day 0
Creatinine level
Measured: Day 24 month
Sodium (Na)
Measured: Day 0
Sodium (Na)
Measured: Day 24 month
Potassium (K)
Measured: Day 0
Potassium (K)
Measured: Day 24 month
Calcium (Ca)
Measured: Day 0
Calcium (Ca)
Measured: Day 24 month
Magnesium (Mg)
Measured: Day 0
Magnesium (Mg)
Measured: Day 24 month
Triiodothyronine (T3)
Measured: Day 0
Triiodothyronine (T3)
Measured: Day 24 month
Free tetraiodothyronine (free T4)
Measured: Day 0
Free tetraiodothyronine (free T4)
Measured: Day 24 month
Thyroxin stimulating hormone (TSH)
Measured: Day 0
Thyroxin stimulating hormone (TSH)
Measured: Day 24 month
Triglycerides
Measured: Day 0
Triglycerides
Measured: Day 24 month
Total cholesterol
Measured: Day 0
Total cholesterol
Measured: Day 24 month
High density lipoprotein cholesterol (HDL)
Measured: Day 0
High density lipoprotein cholesterol (HDL)
Measured: Day 24 month
Low density lipoprotein cholesterol (LDL)
Measured: Day 0
Low density lipoprotein cholesterol (LDL)
Measured: Day 24 month
Vitamine B12 level
Measured: Day 0
Vitamine B12 level
Measured: Day 24 month
Folic acid
Measured: Day 0
Folic acid
Measured: Day 24 month
Rapid plasma reagin for Syphilis test (RPR)
Measured: Day 0
Rapid plasma reagin for Syphilis test (RPR)
Measured: Day 24 month
Mini Mental Status Evaluation (MMSE) total score
Minimu:0, Maximum: 30, Higher scores mean a better outcome.
Measured: Day 0
Mini Mental Status Evaluation (MMSE) total score
Minimu:0, Maximum: 30, Higher scores mean a better outcome.
Measured: Day 24 month
Clinical Dementia Rating Scale (CDR) total score
Minimu:0, Maximum: 3, Higher scores mean a worse outcome.
Measured: Day 0
Clinical Dementia Rating Scale (CDR) total score
Minimu:0, Maximum: 3, Higher scores mean a worse outcome.
Measured: Day 24 month
Hachinski ischemic score total score
Minimu:0, Maximum: 18, Higher scores mean a worse vascular outcome.
Measured: Day 0
Hachinski ischemic score total score
Minimu:0, Maximum: 18, Higher scores mean a worse vascular outcome.
Measured: Day 24 month
Alzheimer's Disease Assessment Scale-cognitive section (ADAS-Cog) total score
Minimu:0, Maximum: 70, Higher scores mean a worse outcome.
Measured: Day 0
Alzheimer's Disease Assessment Scale-cognitive section (ADAS-Cog) total score
Minimu:0, Maximum: 70, Higher scores mean a worse outcome.
Measured: Day 24 month
Alzheimer's Disease Assessment Scale-activities of daily living section (ADCS-ADL) total score
Minimu:0, Maximum: 54, Higher scores mean a better outcome.
Measured: Day 0
Alzheimer's Disease Assessment Scale-activities of daily living section (ADCS-ADL) total score
Minimu:0, Maximum: 54, Higher scores mean a better outcome.
Measured: Day 24 month
Geriatric Depression Scale (GDS) total score
Minimu:0, Maximum: 15, Higher scores mean a worse outcome.
Measured: Day 0
Geriatric Depression Scale (GDS) total score
Minimu:0, Maximum: 15, Higher scores mean a worse outcome.
Measured: Day 24 month
Quality of Life- Alzheimer Dementia (QOL-AD) total score
Minimu:13, Maximum: 52, Higher scores mean a better outcome.
Measured: Day 0
Quality of Life- Alzheimer Dementia (QOL-AD) total score
Minimu:13, Maximum: 52, Higher scores mean a better outcome.
Measured: Day 24 month
MRI examination 1
Total brain volume: MRI examination will be performed on the 1.5 Telsla machine (GE, USA)
Measured: Day 0
MRI examination 2
Total brain volume: MRI examination will be performed on the 1.5 Telsla machine (GE, USA)
Measured: Day 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2021
- Study start23 Sep 2012
- Primary completion12 May 2018
- Study completion23 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Taichung Veterans General 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 163 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taichung Veterans General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tsuo-Hung Lan, Taichung Veterans General Hospital
- Investigators
- Tsuo-Hung Lan, MD, PhD., Principal investigator, National Yang Ming Chiao Tung University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04972643
- Sponsor's protocol ID
- SF12109A
- Status last verified
- Jul 2021
- First submitted
- 8 Feb 2018
- Last updated
- 26 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005 Dec 17;366(9503):2112-7. doi: 10.1016/S0140-6736(05)67889-0.
PubMed 16360788World Alzheimer Report 2010. Alzheimer's Disease International, 2010.
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 2007 Jul;3(3):186-91. doi: 10.1016/j.jalz.2007.04.381.
PubMed 19595937Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES Jr, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline. Ann Intern Med. 2010 Aug 3;153(3):176-81. doi: 10.7326/0003-4819-153-3-201008030-00260. Epub 2010 Jun 14.
PubMed 20547888Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011 Sep;10(9):819-28. doi: 10.1016/S1474-4422(11)70072-2. Epub 2011 Jul 19.
PubMed 21775213Wang XD, Kashii S, Zhao L, Tonchev AB, Katsuki H, Akaike A, Honda Y, Yamashita J, Yamashima T. Vitamin B6 protects primate retinal neurons from ischemic injury. Brain Res. 2002 Jun 14;940(1-2):36-43. doi: 10.1016/s0006-8993(02)02587-8.
PubMed 12020872
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Department of Psychiatry, Taichung Veterans General Hospital
- ClinicalTrials.gov ID
- NCT04972643
- Acronym / sponsor ID
- SF12109A
- Conditions
- Alzheimer Disease, Dementia Disorder
- Keywords
- Dementia Alzheimer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 163 participants (actual)
- Lead sponsor
- Taichung Veterans General HospitalUniversity, hospital or other
- Study start
- 23 Sep 2012 (actual)
- Primary completion
- 12 May 2018 (actual)
- Study completion
- 23 Sep 2018 (actual)
- First posted
- 22 Jul 2021 (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.
Background： Dementia is a progressive, devastating, and fatal neurodegenerative disorder. Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 50% of patients with dementia. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the major bioactive components of n-3 polyunsaturated fatty acids (n-3 PUFAs) , might connect to the etiology of several neuropsychiatric diseases. To our knowledge, it has never been studied to look at the different effects of DHA, EPA and their combination on associated symptoms of AD.
Objectives To examine the effects of DHA, EPA and their combination on associated symptoms of AD, including cognitive function, depressive symptoms, and functional ability.
Method This is a randomized, double-blind, placebo-controlled, 24-month follow-up study, enrolling 200-400 patients with mild AD (Mini-Mental Status Examination (MMSE) 19-26 or Clinical Dementia Rating (CDR) 0.5-1). Cognitive ability is assessed by the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the MMSE. Mood status is assessed by Geriatric Depression Scale (GDS). Functional ability is assessed by the Alzheimer Disease Cooperative Study activities of daily living (ADCS-ADL) and global function by the CDR, quality of life scale (QOL-AD). Brain function is assessed by resting state brain magnetic resonance imaging (MRI).
Detailed description
Background Dementia is a progressive, devastating, and fatal neurodegenerative disorder (Cummings, 2004). As of 2010, there are an estimated 35.6 million people with dementia worldwide. By 2050, it is projected that this figure will have increased to over 115 million (1, 2). Therefore, dementia is not only an important medical disease but also a public health issue to demand immediate attention. A conservative estimate of economic burden from dementia (based on Alzheimer's Society's Dementia United Kindom (UK) report published in February 2007) reaches 20 billion by the year 2010, which suggests an average cost of 25,472 per person annually. It indicated a heavy social financial expense for the whole world in general. Alzheimer's disease (AD) is the most common cause of dementia, accounting for 60-80% of patients with dementia. Given that it is still lacking in effective treatments for AD, there has been growing interest in early detection and prevention for this disastrous illness. Delaying AD onset by 1 year could potentially lower its incidence by more than 9 million cases over the next 40 years (3).
Dementia could be resulted from numerous risk factors and medical conditions including vascular risk factors (e.g. hypertension, diabetes, and obesity), psychosocial factors (e.g. depression), and health behaviors (e.g. physical inactivity and smoking) (4, 5). Indeed, reflecting its heterogeneity, several hypotheses have been proposed for etiology of dementia, including genetic susceptibility, vascular changes, inflammatory process, oxidative stress, and recently, n-3 polyunsaturated fatty acids (n-3 PUFAs) (Fratiglioni et al., 2008;Samieri et al., 2008;Cole and Frautschy, 2010;Mucke and Pitas, 2004;Gomez-Pinilla, 2008). PUFAs are classified into mainly n-3 (or omega-3) and n-6 (or omega-6) groups. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the major bioactive components of n-3 PUFAs, are associated with neuronal membrane stability and fluidity, neurogenesis, neuroplasticity, neurotransmission and anti-inflammation, which might connect to the etiology of several neuropsychiatric diseases including depression and dementia (Horrobin and Bennett, 1999;Su et al., 2000;Chalon, 2006;Lukiw and Bazan, 2006;Su, 2009b;Lin et al., 2010a). On the other hand, arachidonic acid (AA), the major components of n-6 PUFAs, is a precursor of eicosanoids and is important to modulate proinflammatory effects, which might also link to the pathogenesis of neuroinflammatory and neurodegenerative diseases like dementia (Sanchez-Mejia and Mucke, 2010;Lukiw and Bazan, 2010). Consistent with the theoretical relevance, evidences to link PUFAs to dementia have been reported extensively from more epidemiological studies. For example, it has been observed that regions with a high consumption of fish, which are good sources of n-3 PUFAs, appear to have a lower prevalence of dementia (Barberger-Gateau et al., 2002;Barberger-Gateau et al., 2007;Huang et al., 2005;Morris et al., 2003;Kalmijn et al., 1997) and Mild cognitive Impairment (MCI) ;(Roberts et al., 2010)). Although clinical studies until now have failed to demonstrate beneficial effects of n-3 PUFA supplementation in patients with moderate or severe AD (Freund-Levi et al., 2006a;Quinn et al., 2010a), it may benefit in patients with mild AD or MCI and those without apolipoprotein E(APOE) ε4 allele (Freund-Levi et al., 2006b;Chiu et al., 2008;Quinn et al., 2010b). In addition, the two main n-3 PUFAs have different biological effects. DHA is the main n-3 PUFAs in the brain and is important in neuroplasticity and neuroprotection. EPA, on the other hand, is very little in the brain but is important in modulate inflammation and immune function (Lin et al., 2010b;Su, 2009a). To our knowledge, it has never been studied to look at the different effects of DHA, EPA and their combination on different associated symptoms of AD. To provide more evidence for the association between n-3 PUFAs and associated symptoms of AD, including cognitive function, depression, and physical activity in AD, we propose to conduct this double-blind, placebo-controlled, 24-month research. In addition, neuroprotective effects of vitamin B, preliminary findings in recent studies have shown cognitive-protection effects of it among patients with MCI. Moreover, deficiency of vitamin B is known to cause nervousness, depression, and peripheral and central neuropathy. The importance of vitamin B in developmental processes of the brain is supported by the findings that vitamin B deficiency at certain stages of brain development interferes with brain cell proliferation, migration and maturation . Vitamin B affords survival-promoting activities on cultured brain neurons (6). This is probably the first study to evaluate the effects of vitamin B on cognitive protection among Asian patients with AD. Based on the review of the possible benefits from n-3 PUFAs supplement on cognitive function preservation after balancing for its slightest side effects, we here propose a randomized clinical trial study design to test whether Hypothesis Omega-3 PUFAs is protective against cognitive decline among people with mild AD.
Primary Aim To examine whether consumption of n-3 PUFAs protects against cognitive decline in patients with mild AD.
Secondary Aims
- To examine the different effects of DHA, EPA and their combination on different symptoms of AD.
- To examine whether consumption of n-3 PUFAs improves cognitive function in patients with mild AD.
- To examine whether consumption of n-3 PUFAs improves depressive symptoms in patients with mild AD.
- To examine whether consumption of n-3 PUFAs improves physical activity level in patients with mild AD.
Significance of Study
- To provide a simple way through dietary supplement of n-3 PUFAs to prevent cognitive decline and improve depressive symptoms and physical activity in patients with mild AD.
- No placebo-controlled studies regarding n-3 PUFAs in cognitive prevention have been conducted among Asian people.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| EPA and DHA intervention | Experimental | Dietary Supplement: EPA, Dietary Supplement: DHAEPA 1000mg and DHA 1000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. |
| EPA intervention | Experimental | Dietary Supplement: EPAEPA 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. |
| DHA intervention | Experimental | Dietary Supplement: DHADHA 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months. |
Who may qualify
- Ages
- 65 to 105 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (7 listed)
- Patients may be included in the study if they meet the following criteria:
Key exclusion criteria (6 listed)
- Patients may be excluded from the study for any of the following reasons:
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 |
|---|---|---|
| EPAEPA 2000mg Soft capsules | Dietary supplement | EPA and DHA intervention, EPA intervention |
| DHADHA 2000mg Soft capsules | Dietary supplement | DHA intervention, EPA and DHA intervention |
| PlaceboPlacebo Soft capsules | Dietary supplement | Placebo |
Primary outcome
Aspartate Aminotransferase (AST)
Time frame: Day 0
Aspartate Aminotransferase (AST)
Time frame: Day 24 month
Alanine Aminotransferase (ALT)
Time frame: Day 0
Alanine Aminotransferase (ALT)
Time frame: Day 24 month
Albumin level
Time frame: Day 0
Albumin level
Time frame: Day 24 month
Fasting blood glucose
Time frame: Day 0
Fasting blood glucose
Time frame: Day 24 month
Blood Urea Nitrogen (BUN)
Time frame: Day 0
Blood Urea Nitrogen (BUN)
Time frame: Day 24 month
Creatinine level
Time frame: Day 0
Creatinine level
Time frame: Day 24 month
Sodium (Na)
Time frame: Day 0
Sodium (Na)
Time frame: Day 24 month
Potassium (K)
Time frame: Day 0
Potassium (K)
Time frame: Day 24 month
Calcium (Ca)
Time frame: Day 0
Calcium (Ca)
Time frame: Day 24 month
Magnesium (Mg)
Time frame: Day 0
Magnesium (Mg)
Time frame: Day 24 month
Triiodothyronine (T3)
Time frame: Day 0
Triiodothyronine (T3)
Time frame: Day 24 month
Free tetraiodothyronine (free T4)
Time frame: Day 0
Free tetraiodothyronine (free T4)
Time frame: Day 24 month
Thyroxin stimulating hormone (TSH)
Time frame: Day 0
Thyroxin stimulating hormone (TSH)
Time frame: Day 24 month
Triglycerides
Time frame: Day 0
Triglycerides
Time frame: Day 24 month
Total cholesterol
Time frame: Day 0
Total cholesterol
Time frame: Day 24 month
High density lipoprotein cholesterol (HDL)
Time frame: Day 0
High density lipoprotein cholesterol (HDL)
Time frame: Day 24 month
Low density lipoprotein cholesterol (LDL)
Time frame: Day 0
Low density lipoprotein cholesterol (LDL)
Time frame: Day 24 month
Vitamine B12 level
Time frame: Day 0
Vitamine B12 level
Time frame: Day 24 month
Folic acid
Time frame: Day 0
Folic acid
Time frame: Day 24 month
Rapid plasma reagin for Syphilis test (RPR)
Time frame: Day 0
Rapid plasma reagin for Syphilis test (RPR)
Time frame: Day 24 month
Mini Mental Status Evaluation (MMSE) total score
Time frame: Day 0
Minimu:0, Maximum: 30, Higher scores mean a better outcome.
Mini Mental Status Evaluation (MMSE) total score
Time frame: Day 24 month
Minimu:0, Maximum: 30, Higher scores mean a better outcome.
Clinical Dementia Rating Scale (CDR) total score
Time frame: Day 0
Minimu:0, Maximum: 3, Higher scores mean a worse outcome.
Clinical Dementia Rating Scale (CDR) total score
Time frame: Day 24 month
Minimu:0, Maximum: 3, Higher scores mean a worse outcome.
Hachinski ischemic score total score
Time frame: Day 0
Minimu:0, Maximum: 18, Higher scores mean a worse vascular outcome.
Hachinski ischemic score total score
Time frame: Day 24 month
Minimu:0, Maximum: 18, Higher scores mean a worse vascular outcome.
Alzheimer's Disease Assessment Scale-cognitive section (ADAS-Cog) total score
Time frame: Day 0
Minimu:0, Maximum: 70, Higher scores mean a worse outcome.
Alzheimer's Disease Assessment Scale-cognitive section (ADAS-Cog) total score
Time frame: Day 24 month
Minimu:0, Maximum: 70, Higher scores mean a worse outcome.
Alzheimer's Disease Assessment Scale-activities of daily living section (ADCS-ADL) total score
Time frame: Day 0
Minimu:0, Maximum: 54, Higher scores mean a better outcome.
Alzheimer's Disease Assessment Scale-activities of daily living section (ADCS-ADL) total score
Time frame: Day 24 month
Minimu:0, Maximum: 54, Higher scores mean a better outcome.
Geriatric Depression Scale (GDS) total score
Time frame: Day 0
Minimu:0, Maximum: 15, Higher scores mean a worse outcome.
Geriatric Depression Scale (GDS) total score
Time frame: Day 24 month
Minimu:0, Maximum: 15, Higher scores mean a worse outcome.
Quality of Life- Alzheimer Dementia (QOL-AD) total score
Time frame: Day 0
Minimu:13, Maximum: 52, Higher scores mean a better outcome.
Quality of Life- Alzheimer Dementia (QOL-AD) total score
Time frame: Day 24 month
Minimu:13, Maximum: 52, Higher scores mean a better outcome.
MRI examination 1
Time frame: Day 0
Total brain volume: MRI examination will be performed on the 1.5 Telsla machine (GE, USA)
MRI examination 2
Time frame: Day 24 months
Total brain volume: MRI examination will be performed on the 1.5 Telsla machine (GE, USA)
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 Jul 2021.
- Background: PubMed 16360788Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005 Dec 17;366(9503):2112-7. doi: 10.1016/S0140-6736(05)67889-0.
- BackgroundWorld Alzheimer Report 2010. Alzheimer's Disease International, 2010.
- Background: PubMed 19595937Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 2007 Jul;3(3):186-91. doi: 10.1016/j.jalz.2007.04.381.
- Background: PubMed 20547888Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES Jr, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline. Ann Intern Med. 2010 Aug 3;153(3):176-81. doi: 10.7326/0003-4819-153-3-201008030-00260. Epub 2010 Jun 14.
- Background: PubMed 21775213Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011 Sep;10(9):819-28. doi: 10.1016/S1474-4422(11)70072-2. Epub 2011 Jul 19.
- Background: PubMed 12020872Wang XD, Kashii S, Zhao L, Tonchev AB, Katsuki H, Akaike A, Honda Y, Yamashita J, Yamashima T. Vitamin B6 protects primate retinal neurons from ischemic injury. Brain Res. 2002 Jun 14;940(1-2):36-43. doi: 10.1016/s0006-8993(02)02587-8.
- 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.
Tsuo-Hung Lan, MD, PhD. principal investigator
National Yang Ming Chiao Tung University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EPA and DHA in people with Alzheimer Disease and Dementia Disorder, run by Taichung Veterans General 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 7 inclusion and 6 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 Jul 2021. 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. Some participants in this study may receive a placebo. 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?
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?
Aspartate Aminotransferase (AST) (time frame: Day 0). The study lists 56 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04972643, which also lists 6 linked publications.
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 Jul 2021.