operations, including research ethi

operations, including research ethics board communications and protocol approvals, staff training, site visits, data management, and they followed current Good Clinical
Practice, the Declaration of Helsinki guidelines, and research ethics board guidelines and requirements. The study protocol was approved by the Canadian SHIELD Ethics Review Board. Pivotal Therapeutics Inc. (Woodbridge, Ontario, Canada) sponsored the study. This 8-week study was a multicenter, randomized, double-blinded, placebo-controlled study that investigated
LC n-3 PUFA nutritional deficiency and its correction with 4 g/day of corn oil or 6:1-OM3 formulations (Supplied by Pivotal Therapeutics Inc). Ambulatory cardiovascular subjects were questioned and screened for their eligibility into the trial. Male and female study subjectsC18 years of age, with one or more risk factor for CVD, were deemed eligible for study enrollment if their fasting whole blood OS levels were6.1 % by weight of total blood fatty acid
levels, and their serum TG was between 1.02 and 5.65 mmol/L. Subjects were excluded from the study if they refused to provide informed consent, had a known allergy to fish, were premenopausal women, were currently taking hormone replacement therapy (HR), lipid-altering
medication or LC n- PUFA supplements, had a history of alcohol abuse, were medically ill, had a history of ventricular arrhythmia, bleeding or clotting disorder, liver or kidney disease, autoimmune disorder or suppressed immune systems, myopathy or rhabdomyolysis, seizure
disorder, or had an implantable cardioverter defibrillator. Subjects on a stable statin medication for a minimum of three months were eligible to enroll. All eligible subjects were randomized using a list generated by the CRO (random assignment of ‘‘Treatment A’’,
or ‘‘Treatment B’’), to receive four 1 g capsules per day of either corn oil (placebo) or 6:1-OM3 (providing a minimum of 2.72 g/day of EPA and 440 mg/day of DHA). Corn oil
was almost completely devoid of LC n-3 PUFA and mostly consisted of n-6 & n-9 fatty acids (linoleic 59 %; oleic 25 %; palmitic 11 %; stearic 2 %), while 6:1-OM3 contained over 94 % LC n-3 PUFA and less than 5 % n-6 fatty acids. Both treatment capsules were indistinguishable from
one another, and packaged by a third party in white identical boxes labeled ‘‘Treatment A’’ or ‘‘Treatment B.’’ Subjects were stratified by their baseline TG levels into two Cohorts.
Cohort 1 included subjects with normal to marginally high TG levels (1.02–2.25 mmol/L representing 90–199 mg/dL) and Cohort 2 included subjects with hypertriglyceridemia
(2.26–5.65 mmol/L representing TG 200–500 mg/dL). Randomization was on a 1:1 basis to ensure approximately equal numbers of subjects in each of the two treatment arms. All investigators, the CRO, and the study sponsor, remained blinded to the treatment regimen during the
study’s progress. The primary end point of the study was to determine the efficacy of the 6:1-OM3 treatment to correct LC n-3 PUFA deficiency, by measuring the placebo-adjusted change in
blood OS and OI levels post-treatment. Secondary outcome measures included changes in serum levels of TG, VLDLC, IDL-C, LDL-C, HDL-C, apo-A, apo-B, total cholesterol (TC), high sensitivity C-reactive protein (hs-CRP), arachidonic acid (AA):EPA ratio, n-6:n-3 ratio, and fasting
blood glucose from the study baseline to the study end point after 8 weeks of treatment.
Treatment schedule and subject evaluation Enrolled subjects provided the baseline 12-hour fasting blood specimens for analyses and completed the health assessment forms. In addition, subject weight, body mass index (BMI), waist and hip circumference and blood pressure were measured and recorded in case report forms. Subsequent to the collection of baseline blood specimens, enrolled subjects were stratified as Cohort 1 or Cohort 2
based upon their fasting TG levels obtained at the screening evaluation. Subjects in each Cohort were provided with 4 capsule/day doses of either Treatment A or B for 8 weeks. All subjects provided 10–12-hour fasting blood specimens by venipuncture at week 0 (baseline) and after 4
and 8 weeks of treatment. The samples were sent for analyses of the primary and secondary measures, as described below. In addition, health assessments (weight, BMI, blood pressure), capsule compliance evaluation, and adverse events reporting were measured, and reported at
each subsequent clinic visit. An emergency number was provided to each study participant for reporting any serious adverse reaction during the entire study period. Sample analysis Analyses of total blood fatty acids levels, including OS, OI, AA:EPA ratio, n-6:n-3 ratio and fasting blood glucose were performed at a central laboratory, (University Health Network, Specialty Laboratory, Toronto, Ontario, Canada), accredited by the College of American Pathologists’ Laboratory Accreditation Program. The fatty acid compositions of whole blood were determined on 200 ll of sample after lipid extraction by a modification of the method of Bligh and Dyer [33]. The total lipid fraction was then methylated with 12 % (w/w) boron trifluoride in methanol
by incubation at 90C for 25 min to produce fatty acid methyl-esters (FAME). After cooling, the FAME were extracted with hexanes, washed with water, dried under nitrogen and dissolved in hexanes. The fatty acid composition was then determined by GLC performed on a 100 m
Varian Select TM FAME CP7420 capillary column (0.25 mm i.d.), using an Agilent Technologies 6890 N

Hasil (Bahasa Indonesia) 2:

operasi, termasuk etika penelitian komunikasi papan dan persetujuan protokol, pelatihan staf, kunjungan lapangan, manajemen data, dan mereka mengikuti Baik klinis saat
Practice, Deklarasi pedoman Helsinki, dan pedoman penelitian etika dewan dan persyaratan. Protokol penelitian telah disetujui oleh Canadian SHIELD Etika Review Board. Penting Therapeutics Inc (Woodbridge, Ontario, Kanada) yang disponsori penelitian. Studi 8-minggu ini adalah multisenter, acak, plasebo-terkontrol studi buta ganda yang diselidiki
LC n-3 PUFA kekurangan gizi dan koreksi dengan 4 g / hari minyak jagung atau 6: 1-OM3 formulasi (Disediakan oleh Penting Therapeutics Inc). Subyek kardiovaskular rawat ditanyai dan disaring untuk kelayakan mereka ke persidangan. Pria dan wanita studi subjectsC18 tahun, dengan satu atau lebih faktor risiko untuk penyakit kardiovaskular, yang dianggap memenuhi syarat untuk pendaftaran studi jika tingkat OS puasa seluruh darah mereka 6,1% berat asam lemak darah jumlah
tingkat, dan serum mereka TG adalah antara 1,02 dan 5,65 mmol / L. Subyek dikeluarkan dari penelitian jika mereka menolak untuk memberikan persetujuan, memiliki alergi diketahui ikan, adalah perempuan premenopause, yang saat ini sedang terapi penggantian hormon (SDM), lipid-altering
obat atau LC n suplemen PUFA, memiliki riwayat penyalahgunaan alkohol, sakit medis, memiliki sejarah aritmia ventrikel, perdarahan atau gangguan pembekuan, hati atau penyakit ginjal, gangguan autoimun atau sistem kekebalan tubuh ditekan, miopati atau rhabdomyolysis, kejang
gangguan, atau memiliki defibrilator cardioverter implan. Subyek pada obat statin yang stabil selama minimal tiga bulan yang memenuhi syarat untuk mendaftar. Semua mata pelajaran yang memenuhi syarat secara acak menggunakan daftar yang dihasilkan oleh CRO (tugas acak '' Pengobatan A '',
atau '' Pengobatan B ''), menerima empat 1 g kapsul per hari baik minyak jagung (plasebo) atau 6: 1-OM3 (menyediakan minimal 2,72 g / hari EPA dan 440 mg / hari DHA). Minyak jagung
hampir benar-benar tanpa LC n-3 PUFA dan sebagian besar terdiri dari n-6 & n-9 asam lemak (linoleat 59%; oleat 25%; palmitat 11%, stearat 2%), sedangkan 6: 1-OM3 terkandung lebih dari 94% LC n-3 PUFA dan asam n-6 asam lemak kurang dari 5%. Kedua kapsul pengobatan yang bisa dibedakan dari
satu sama lain, dan dikemas oleh pihak ketiga dalam kotak putih identik berlabel '' Pengobatan A '' atau '' Pengobatan B. '' Subyek dikelompokkan berdasarkan dasar tingkat TG mereka menjadi dua Kohort.
Cohort 1 termasuk subyek dengan sedikit tinggi normal kadar TG (1,02-2,25 mmol / L mewakili 90-199 mg / dL) dan Cohort 2 termasuk subyek dengan hipertrigliseridemia
(2,26-5,65 mmol / L mewakili TG 200-500 mg / dL). Pengacakan adalah pada 1: 1 basis untuk memastikan jumlah kira-kira sama mata pelajaran di masing-masing dua kelompok pengobatan. Semua peneliti, CRO, dan sponsor studi, tetap buta terhadap rejimen pengobatan selama
kemajuan studi. Tujuan utama dari penelitian ini adalah untuk menentukan kemanjuran dari 6: pengobatan 1-OM3 untuk memperbaiki LC n-3 PUFA kekurangan, dengan mengukur perubahan plasebo-disesuaikan
OS darah dan kadar OI pasca perawatan. Ukuran hasil sekunder termasuk perubahan tingkat serum TG, VLDLC, IDL-C, LDL-C, HDL-C, apo-A, apo-B, kolesterol total (TC), protein tinggi sensitivitas C-reaktif (hs-CRP) , asam arakidonat (AA): rasio EPA, n-6: n-3 rasio, dan puasa
. glukosa darah dari baseline studi ke titik akhir penelitian setelah 8 minggu pengobatan
jadwal Pengobatan dan subjek evaluasi Terdaftar pelajaran disediakan baseline 12- jam puasa spesimen darah untuk analisis dan menyelesaikan bentuk pemeriksaan kesehatan. Selain itu, berat badan subjek, indeks massa tubuh (BMI), pinggang dan lingkar pinggul dan tekanan darah diukur dan dicatat dalam bentuk laporan kasus. Setelah koleksi spesimen darah awal, terdaftar pelajaran dikelompokkan sebagai Cohort 1 atau 2 Cohort
berdasarkan puasa mereka tingkat TG diperoleh pada evaluasi skrining. Subjek dalam setiap Cohort diberikan dengan dosis 4 kapsul / hari baik Pengobatan A atau B selama 8 minggu. Semua mata pelajaran yang disediakan 10-12 jam spesimen darah puasa dengan venipuncture pada minggu 0 (baseline) dan setelah 4
dan 8 minggu pengobatan. Sampel dikirim untuk analisis tindakan primer dan sekunder, seperti yang dijelaskan di bawah ini. Selain itu, pemeriksaan kesehatan (berat badan, BMI, tekanan darah), evaluasi kepatuhan kapsul, dan efek samping pelaporan diukur, dan dilaporkan pada
setiap kunjungan klinik berikutnya. Nomor darurat yang diberikan kepada masing-masing peserta studi untuk melaporkan setiap efek samping yang serius selama masa penelitian. Analisis sampel Analisis total tingkat asam lemak darah, termasuk OS, OI, AA: EPA rasio, n-6: n-3 rasio dan glukosa darah puasa dilakukan di laboratorium pusat, (Universitas Health Network, Laboratorium Khusus, Toronto, Ontario , Kanada), diakreditasi oleh College of Program Akreditasi Laboratorium Amerika Patolog '. Komposisi asam lemak dari seluruh darah ditentukan pada 200 ll sampel setelah ekstraksi lipid dengan modifikasi metode Bligh dan Dyer [33]. Fraksi lipid Total kemudian termetilasi dengan 12% (b / b) boron trifluorida dalam metanol
dengan inkubasi pada 90? C selama 25 menit untuk menghasilkan asam lemak metil ester-(FAME). Setelah pendinginan, FAME yang diekstraksi dengan heksana, dicuci dengan air, dikeringkan di bawah nitrogen dan dilarutkan dalam heksana. Komposisi asam lemak kemudian ditentukan oleh GLC dilakukan pada 100 m
Varian Pilih TM FAME CP7420 kolom kapiler (0,25 mm id), menggunakan Agilent Technologies 6890 N