Clinical trial NCT02947100: Omega-3 Fatty Acids in Sickle Cell Disease
Official title: Phase I/II Safety and Dose Escalation Trial of the Omega-3 Fatty Acids Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) in Children and Young Adults With Sickle Cell Disease (SCD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
omega-3 fatty acids
Docosahexaenoic Acid (DHA)
Eicosapentaenoic Acid (EPA)
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
name: Thomas Jefferson University
name: Solutex GC S.L.
First posted: 2016-10-27
Enrollment: 4
Sex: ALL
Minimum age (years): 8
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety of a new formulation of the omega-3 fatty acids Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) and to assess whether it decreases inflammation and inflammatory pain in children and young adults with Sickle Cell Disease.


Eligibility criteria: Inclusion Criteria:

Subjects who meet all of the following criteria are eligible for enrollment into the study:

* Participant has signed the informed consent/assent with parent signing informed consent as age appropriate.
* Established diagnosis of HbSS, HbSC or HbSβo Thalassemia
* History of ≥1 vasoocclusive events (managed at home and/or in hospital) in preceding 12 months.
* Regular compliance with comprehensive care.
* Aged 8 years or greater and less than 26 years.
* At enrollment, subject should be in his/her baseline steady state and not in the midst of any acute complication due to SCD. Must be at least 2 weeks from infection or vasoocclusive crisis at time of screening labs

Exclusion Criteria:

* Baseline hemoglobin levels \<5.5 gm/dL.
* Inability to swallow capsules
* Poor compliance with previous treatment regimens.
* Hepatic dysfunction
* Renal dysfunction
* PT and/or PTT ≥ 20% outside of normal
* Allergy to fish, shell fish or soy
* Triglyceride levels \<80mg/dL.
* Pregnancy.
* Chronic Transfusion Therapy.
* Transfusion within the last 30 days.
* Treatment with any investigational drug or regular fish oil supplementations in last 60 days.
* Currently receiving another investigational agent, or on such an agent with the last 60 days.
* Dosage changes in preceding 3 months if on hydroxyurea
* Diagnosed bleeding disorder or patient on concomitant anti-coagulation.
* Conditional or abnormal result on most recent transcranial doppler or history of stroke.
* Other active chronic illness that could adversely affect subjects performance
* Children in Care
* Platelet count less than 100,000

Primary outcomes:
measure: Clinical Safety, in a Dose Escalation Trial of SCD-Omegatex™ as Evidenced by an Absence of Adverse Events.
timeFrame: 6 months with continuous monitoring
measure: Determine Whether 6 Months of Supplementation With SCD-Omegatex™ Will Reduce Thermal Sensitivity by Quantitative Sensory Testing to Below Pre-treatment Levels
timeFrame: 6 months
Secondary outcomes:
measure: Health-associated Quality of Life
timeFrame: 6 months
measure: Number of Days With Pain Measured by iPad Daily Report Pain Calendar
timeFrame: 8 months
measure: Changes in Individual Thermal Sensitivity Thresholds by QST
timeFrame: 8 months
Other outcomes:
measure: Thrombin Generation as Assessed by Calibrated Automated Thrombogram
timeFrame: 6 months
measure: High Sensitivity C-reactive Protein (mg/L)
timeFrame: 6 months
measure: Plasma Lipidomic Analysis
timeFrame: 6 months
measure: Urine Resolvin D1 (pg/mg Creatinine)
timeFrame: 6 months
measure: Plasma Levels of Lactate Dehydrogenase (IU/L)
timeFrame: 6 months
measure: Fetal Hemoglobin (%)
timeFrame: 6 months
measure: Analysis of Pro and Anti-inflammatory Cytokines in Plasma Including Interleukin (IL)1-beta, IL-4, IL-6, IL-8, IL-10 and Tumor Necrosis Factor (TNF) Alpha ( pg/ml)
timeFrame: 6 months
measure: Plasma Endothelin-1(pg/ml)
timeFrame: 6 months
measure: Plasma Levels Soluble Vascular Adhesion Molecule -1 (VCAM-1) (ng/ml)
timeFrame: 6 months
measure: Plasma Levels of Soluble P-selectin (ng/ml)
timeFrame: 6 months
measure: Plasma Levels of Soluble L-selectin (ng/ml)
timeFrame: 6 months
measure: Hemostatic Markers in Plasma Including D-dimers and Prothrombin Fragment 1.2 (Nmol/L)
timeFrame: 6 months
Locations:
city: Wilmington
country: United States
facility: Nemours/Alfred I duPont Hospital for Children
state: Delaware
Study officials:
affiliation: Nemours Children's Clinic
name: Robin E Miller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Daak AA, Ghebremeskel K, Hassan Z, Attallah B, Azan HH, Elbashir MI, Crawford M. Effect of omega-3 (n-3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2013 Jan;97(1):37-44. doi: 10.3945/ajcn.112.036319. Epub 2012 Nov 28.
citation: Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol. 2007;25:101-37. doi: 10.1146/annurev.immunol.25.022106.141647.
citation: Calder PC. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2015 Apr;1851(4):469-84. doi: 10.1016/j.bbalip.2014.08.010. Epub 2014 Aug 20.
citation: Tomer A, Kasey S, Connor WE, Clark S, Harker LA, Eckman JR. Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids. Thromb Haemost. 2001 Jun;85(6):966-74.