Omega-3 Fatty Acids in Sickle Cell Disease

Sickle Cell Disease Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02947100
• Other study ID #: RM002
• Secondary ID: P20GM109021
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 25, 2018
• Est. completion date: October 15, 2018

Study information

• Verified date: September 2020
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: October 15, 2018
• Est. primary completion date: October 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 25 Years

Eligibility

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 HbSßo 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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• SCD-Omegatex™
Subjects will receive SCD-Omegatex™ (Enteric Fish Oil 250 DHA/27 EPA Soft Gelatin Capsule, 450 mg) at one of two daily doses, orally, once a day for 6 months. The trial will follow a "3+3" design using two dose levels. In the phase I portion, subjects will be treated with a dose of 25 mg/kg/day DHA and EPA. If this is tolerated without dose limiting toxicity (DLT), a subsequent cohort of patients will be treated at a dose of 37.5 mg/kg/day with a maximum total daily dose of 4 grams. Once a maximum tolerated dose (MTD) is determined, subjects on the phase II portion of the study will be treated at that dose.

Locations

Country	Name	City	State
United States	Nemours/Alfred I duPont Hospital for Children	Wilmington	Delaware

Sponsors (4)

Lead Sponsor	Collaborator
Robin E. Miller	National Institute of General Medical Sciences (NIGMS), Solutex GC, S.L., Thomas Jefferson University

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Review. — View 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. — View Citation

Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol. 2007;25:101-37. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Thrombin Generation as Assessed by Calibrated Automated Thrombogram	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	High Sensitivity C-reactive Protein (mg/L)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Plasma Lipidomic Analysis	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Urine Resolvin D1 (pg/mg Creatinine)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Plasma Levels of Lactate Dehydrogenase (IU/L)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Fetal Hemoglobin (%)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	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)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Plasma Endothelin-1(pg/ml)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Plasma Levels Soluble Vascular Adhesion Molecule -1 (VCAM-1) (ng/ml)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Plasma Levels of Soluble P-selectin (ng/ml)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Plasma Levels of Soluble L-selectin (ng/ml)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Other	Hemostatic Markers in Plasma Including D-dimers and Prothrombin Fragment 1.2 (Nmol/L)	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Primary	Clinical Safety, in a Dose Escalation Trial of SCD-Omegatex™ as Evidenced by an Absence of Adverse Events.	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months with continuous monitoring
Primary	Determine Whether 6 Months of Supplementation With SCD-Omegatex™ Will Reduce Thermal Sensitivity by Quantitative Sensory Testing to Below Pre-treatment Levels	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Secondary	Health-associated Quality of Life	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	6 months
Secondary	Number of Days With Pain Measured by iPad Daily Report Pain Calendar	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	8 months
Secondary	Changes in Individual Thermal Sensitivity Thresholds by QST	No results are available from any outcome measures as study was stopped early due to manufacturing issues with study drug and will not be reopened.	8 months