Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04386525 |
| Other study ID # |
002518 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2020 |
| Est. completion date |
February 1, 2022 |
Study information
| Verified date |
May 2020 |
| Source |
King Fahad Medical City |
| Contact |
Nauf Almansour, Stroke Consultant |
| Phone |
+96653 941 7892 |
| Email |
nalmansour.stroke[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In this trial, The investigators are going to investigate the improvement of neurological
functions and infarced area of the brain in ischemic stroke patients after ingestion of omega
3 products that have high concentrations of DHA and EPA in comparison to control group. The
study will assess the improvement by computerized calculation of the size of the infarcted
area before and after the intervention and neurological assessment tools. The researchers
will follow the scientific and ethical regulations prevent any harmful effect on recruited
subjects.
Description:
Introduction and Background According to the Center of Disease Control and Prevention, stroke
is the 5th leading cause of mortality in the US, and a leading cause of significant long-term
disability where almost 50% of stroke survivors, age 65 and above, suffer from disabling
decrease in mobility. In its simplest form, an ischemic stroke is a decrease in the blood
flow to a certain area in the brain, due to a clot, stenosis or other cause, which lasts long
enough to cause permanent cellular injury and death and by extension, disability [1].
However, much more goes into that process.
The decreased blood flow to the tissue leads to the primary insult caused by ischemia which
leads to direct and immediate cell death. Meanwhile, the tissue surrounding this ischemic
area gets affected by the inflammation in the ischemic area, but maintains its viability and
is called the penumbra. Later on, this penumbra gets affected by the immune response and
toxic inflammatory mediators released in the ischemic area. Which ultimately results in
axonal structural changes and subsequent neuronal damage (secondary insult.) The main
attention of this paper is looking into the prevention of secondary insult and preserving the
penumbra which carries a neurorestorative capacity that is diminished by the inflammatory
response and the possibility of restoring the damaged area by neurogenesis as will be
explained later. As a result, improving the disability caused by the ischemic event [2].
Currently, the only FDA approved treatments of stroke are Tissue Plasminogen Activator (tPA)
and Trevo which is a clot removal device, introduced in 2012. However, the group harvesting
the benefits of those treatments are fairly limited. For example, tPA has many
contraindications in addition to a narrow window of application of 4.5 hours from the start
of symptoms. Trevo can only be used within 6 hours as well (extended to 24h in certain cases)
[3]. Furthermore, a major downside that plagues these interventions is the
ischemia/reperfusion injury. I/R injury is characterized by reduced vascular relaxation and
perfusion, increased macromolecular permeability and an intense inflammatory response derived
by reactive oxygen species (ROS) from the ischemic area [2].
Other interventions are being currently studied in the preclinical setting which is aimed at
enhancing and supporting the activity of neurons and neural progenitor cells and promoting
long-term functional recovery. Rather than concentrating on restoring blood flow, these
interventions are aimed towards inducing neuroprotection and saving brain function in the
long term. One such example, is omega-3 essential polyunsaturated fatty acids (PUFA n3)
specifically docosahexaenoic acid (DHA, 22:6, n-3) and eicosapentaenoic acid (EPA, 20:5,
n-3), to a lesser extent. They have been shown to have a profound effect on decreasing the
neuroinflammation in the brain tissue of animal models after an acute stroke in addition to
its positive effects on cognitive function and neurodevelopment [4,5]. Furthermore, studies
conducted on mice such as the one conducted by José Pedro De La Cruz et al has shown great
neuroprotective qualities and a significant reduction in post-stroke neuroinflammation using
olive oil and acetylsalicylic acid [6].
Considering all that which have been mentioned in our introduction, the investigators have
set several objectives for this paper. First of all, studying the effects of using * omega-3*
as a safe and effective measures to prevent neuroinflammation after an ischemic event and how
can this affect the process of neurogenesis and subsequently and effect on patient disability
by using olive oil as one of the resources of omega-3.
Research Design :
The study will be an open-labelled two-armed randomized control trial, phase 4. One arm will
receive the intervention (fish oil). The other arm will be the control.
Population and Sample:
The setting of our study will be the KFMC ASU and NCCU. Our target population will be an
ischemic stroke, non-hemorrhagic, reperfused, and non-complicated stabilized patients
admitted to the NCCU/ASU at KFMC stroke unit located in Riyadh, Saudi Arabia. Regarding the
sample size, it will consist of 60 stroke patients /year compiled of 5 patients each month.
The investigators will put into consideration having a confidence level of 95% with a power
of 80%. So, the number of the sample might be changed slightly according to the rate of
encountered eligible patients.
Plan of Subject's recruitment:
The investigators are going to recruit confirmed admitted ischemic stroke patients from the
emergency department then referred to the stroke unit (NCCU/ASU) who need to follow up or
close monitoring. Patients will be eligible after stabilization and reperfusion to minimize
any risks to our intervention. This process will be monitored by the ICU specialist and a
neurologist. The intervention will not be started until the specialists approve to start.
More importantly, the subject will not be recruited until they or their responsible relative
gives informed consent. Participants can withdraw at any time during the trial.
Plan of data collectors' recruitment:
Data collectors will be from health-care-related specialities
Randomization :
Patients will be randomized by the order of their arrival to the NCCU/ASU alternating between
intervention and control groups with every patient. A research team member will be assigned
to put patients that arrive at the NCCU/ASU in either of the 2 groups using a computer
program which randomly selects between A or B. The fact of which letter is assigned to which
group will also be chosen by the same researcher and stored on an excel sheet which only
he\she has access to.
Blinding :
The study will be an open-label randomized trial due to the difficulty of blinding the
patients and physicians from the odour, taste and colour between the intervention and
control.
Intervention Details:
Generally, the supplement (but not the placebo) will come in the form of an encapsulated soft
gel which will be administered through the nasogastric or orogastric tube by injecting it in
the nutrition bag and dividing the dose throughout the number of bags per day.
The average length of stay in ischemic stroke patients is 28 days, thus, the intervention
group will receive fish oil for 1 month starting from the incidence of the stroke. [13] The
chosen product of intervention is OMACOR from Abbott brand. This product is registered in the
Saudi FDA and is available in the market.
The investigators will administer 4g per day of fish oil three times with meals for one month
with monitoring the health status regularly. According to the European Food Safety Authority
in 2012, long-term consumption of EPA and DHA supplements at combined doses of up to about 5
g/day, or EPA alone up to 1.8 g/day appears to be safe for the adult population and does not
increase the risk of spontaneous bleeding episodes, or affect glucose homeostasis, immune
function or lipid peroxidation. [18]
Mechanism:
Until the time of this study, the full mechanism of action of omega 3 is not well understood
to explain all of its effects. However, some theories to how it lowered blood triglyceride
levels propose that it reduces the hepatic production of triglyceride-rich very-low-density
lipoproteins. It also suppresses adipose tissue inflammation and increases FA uptake in
adipose, heart, and skeletal muscle. On the cellular level, it inhibits the action of acyl
CoA:1,2 diacylglycerol acyltransferase, increase hepatic mitochondrial and peroxisomal
beta-oxidation and thus result in a reduction in the hepatic synthesis of triglycerides
lowering their blood levels1. Furthermore, its cardiovascular effects are considered
multifactorial. It inhibits platelet aggregation, increases circulating EPA/arachidonic acid
ratio, and increases EPA composition from carotid plaques. [14]
Safety :
From a safety standpoint, omega 3 is a very safe drug with mild or no symptoms at all. The
only serious dangerous side effect is an allergic reaction to the drug. some side effects
include headache, unpleasant taste, bad-smelling sweat, bad breath, and gastrointestinal
symptoms such as heartburn, nausea, and diarrhoea. [15] Besides, omega 3 being a mild
platelet aggregation inhibitor, it potentiates the effects of antiplatelet like low dose
(baby) aspirin. The interaction was reported in a case report
paper. Thus, after administering omega 3 or changing the dose for a patient on baby aspirin
or warfarin, the INR should be checked. [14]
Monitoring :
While administering omega 3, some parameters should be monitored at baseline and
periodically. In patients with hepatic impairment monitor liver function tests and enzymes
particularly ALT. Signs or symptoms of bleeding and perform an INR both at baseline and
periodically. [14]
Drug Administration :
In our study, the investigators expect that some patients might be fully dependent on feeding
tubes. However, the omega 3 pills could still be administered through NGT or through feeding
formulas that contain EPA and DHA. In the study by Julie M. [15] Martin et al. found no
difference in the clinical outcome in critically ill patients when administering the drug
through NGT vs feeding formulas. However, administering pills instead of feeding formulas is
more convenient regarding training the staff and determining doses in addition to being
cost-effective. [16]
Data collection, Follow-up and Communication :
The neurology consultant (the principal investigator) will directly supervise the data
collection, intervention, follow-up and communication with the help of medical professionals
co-investigators and nurses. Meanwhile, entering the data and monitoring adverse effects will
be assessed by clinical pharmacists and other co-investigators. The participants will have
the contact number of the principal investigator to report any news or adverse reactions
Criteria for stopping follow-up and intervention in the subject:
Some events will cause stopping and loss of follow-up such as :
1. Enlarging stroke area
2. Deterioration of the case condition (e.g. loss more neurological functions and
consciousness or other systematic organs)
3. New onset of stroke in the same or different areas
4. Participant withdrawing
5. Death or brain death
Analysis :
The investigators will analyze the data using the SPSS software program (version 25).
Descriptive analysis and statistical Drop-outs from the study will be excluded from the
analysis, so the analysis type will be "per protocol analysis".
