Clinical trial NCT03926351: High Dose Omega 3 in People at Risk for Dementia
Official title: A Randomized, 24 Week Parallel-group Placebo-controlled (Phase 2) Pilot-study of High Dose Omega 3 (DHA) in People at Risk for Dementia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Dementia
Inflammation
Mild Cognitive Impairment
Cognitive Decline
SCD
Cognitive Dysfunction
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorder
Cognition Disorders
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
Collaborators: name: BASF AS
name: Pre Diagnostics AS
First posted: 2019-04-24
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, 24-week parallel-group placebo-controlled (Phase 2) pilot-study of high dose Omega 3 (DHA) in people at risk for dementia
Primary purpose: PREVENTION

Brief summary: The aim of this study is the efficacy of a docosahexaenoic acid (DHA)-rich dietary supplement in improving key dementia-related mechanisms and cognitive function in older people at risk for dementia. This is a randomized placebo-controlled, 24 weeks, phase 2 study of Omega 3 in people with increased risk of dementia. The aim is to explore the effects of DHA on cognitive performance (CERAD 10 word memory tests, TMT A/B, Stroop Color-Word, FAS, VOSP silhouettes, Cantab-test (RT, PAL, SWT)), biological markers (blood: CRP, NLF, TNF-alpha, MCI-1, PBMC Abeta middomain, Omega-3-index, IL, CSF: NLF, sTREM2, Ab 1-42, total and -phospho-tau) and imaging (MRI: standard structural DDI protocol including Freesurfer and WML measurements, DTI and ASL).

Detailed description: Earlier trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been moderately promising, but these interventions often suffered from relatively low DHA concentrations. In this trial, the investigators will use a DHA-rich dietary supplement formulated using a self-microemulsifying delivery system to accelerate absorption.

Modification of innate immune activity has already been seen using DHA-rich supplements, and this type of intervention has been shown to ameliorate AD-associated PBMC profiles, and to be associated with improvements in cognition. DHA can cross the BBB, and the resulting CSF concentrations are associated with reduced CSF total tau levels indicating that DHA reduce neurodegeneration, ameliorate Abeta42 induced neuronal damage, and increase microglia Abeta phagocytosis. However, pre-clinical and pre-dementia intervention trials linked to biomarkers for the AD disease process is lacking, and therefore, stratification with respect to stage of disease process has not been performed.

Study cohort: subjects in this pilot study will be recruited from the Norwegian Dementia Disease Initiative (DDI) cohort. The DDI cohort consists of 600 participants with Subjective Cognitive Dedcline (SCD), Mild Cognitive Impairment (MCI) and normal control subjects that have been included at dementia centres across Norway during 2012-2016. Blood samples and cerebrospinal fluid (CSF) have been collected and are stored centrally at Ahus. A comprehensive and highly standarized clinical assessment program has been administered by trained raters (assessors). The investigators are currently performing 2-year follow-up evaluations. Genetic data including APOE-isoforms have been collected as have baseline and follow-up MRIs, PET scans (so far in Oslo and Bergen) and baseline CSF examinations (Ab, total-tau and phosphorus-tau). Cognitive assessments at baseline and follow-up include MMSE and Clinical Dementia Rating (CDR), CERAD 10 word memory test, Clock drawing test, Trail Making Test A and B, Verbal fluency test (FAS), visual recognition test (VOSP silhouettes), Stropp Coloraturas-Word. Data is assembled in a customised database (UiO secure server (TSD)), developed based on XNAT (http://www.xnat.org) and also connected to pipelines for image analysis. A selection from CANTAB MCI test battery including RTI (reaction time), PAL (paired associates learning test), and SWM (spatial working memory).

Study design: All subjects included in the intervention study will have completed 2-year follow-up in the DDI study prior to inclusion and will be on stable medication at least 3 months prior to baseline examinations. Based on the existing electronic CRF for DDI, social e-RCT-CRFs will be developed and programmed into the proprietary XNAT database. Patients fulfilling the inclusion criteria will be identified by a nurse at the memory outpatient clinics and will be given a short information letter regarding the study. Written consent will be asked for. Thereafter, a medical and neurological examination of the patient will be performed, including a medical history and medication use.

This initial pilot study is a minor feasibility study with 40 subjects randomised equally to either of 2 treatment groups for 24 weeks,

Omega-3 3 capsules/day Placebo 3 capsules/day

Each study participant will take 3 capsules in the morning for the 24-week study period. The study may be followed by a larger and statistical valid study. Patients will be randomized (by means of a computerized program) to identically appearing set of capsules with Omega-3 or placebo, 1:1 (produced by BASF AS).

Optional extension study: Participants will be offered another 24-week Omega-3 capsule supply after study end, and a follow-up assessment after 1 year will be conducted, comparing those with and without continuous Omega-3 treatment.

Eligibility criteria: Inclusion Criteria:

* Age \> 50 years
* SCD or MCI
* No evidence of neurodegeneration (i.e. CSF phospho and total tau-levels below cut-off)
* Scandinavian mother tongue
* Completed 2-year follow-up in the DDI-study
* Stable medication for at least 3 months prior to baseline exam

Exclusion Criteria:

* Dementia (defined as MMSE \< 26 and/or CDR \>/= 1))
* Other dementia giving disease than AD
* Other brain disease
* Significant depression
* Unstable coronary heart disease or heart failure in need of treatment
* Systemic inflammatory diseases
* Somatic disease that might affect cognitive function adversely
* Usage of anticoagulants
* Prior radiation- or chemo-therapy possibly affecting CNS
* Relevant cancer or other serious disease with expected survival \< 5 years
* Fish meal intake more than 2 times a week
* Regularly intake of Omega-3 supplements over the last 3 months

Primary outcomes:
measure: Cognitive function
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Cognitive function
timeFrame: Baseline to 24 weeks
measure: Cognitive function
timeFrame: Baseline to 24 weeks
measure: Cognitive function
timeFrame: Baseline to 24 weeks
measure: Blood PBMC betaAmyloid mid-domain assay
timeFrame: Baseline to 24 weeks
measure: CSF betaAmyloid 1-42
timeFrame: Baseline to 24 weeks
measure: CSF TAU
timeFrame: Baseline to 24 weeks
measure: CSF Phospho-TAU
timeFrame: Baseline to 24 weeks
measure: MRI ASL
timeFrame: Baseline to 24 weeks
measure: MRI WML
timeFrame: Baseline to 24 weeks
measure: MRI DTI
timeFrame: Baseline to 24 weeks
Other outcomes:
Locations:
city: Lørenskog
country: Norway
facility: Akershus university hospital, Sykehusveien 25
Study officials:
affiliation: University Hospital, Akershus
name: Tormod Fladby, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: