Omega-3 Fatty Acids in Sickle Cell Disease

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)

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02947100

Enrollment

Registered

2016-10-27

Start date

2018-01-25

Completion date

2018-10-15

Last updated

2020-10-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease, omega-3 fatty acids, Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid (EPA)

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.

Interventions

DRUGSCD-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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

8 Years to 25 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Clinical Safety, in a Dose Escalation Trial of SCD-Omegatex™ as Evidenced by an Absence of Adverse Events.	6 months with continuous monitoring	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.
Determine Whether 6 Months of Supplementation With SCD-Omegatex™ Will Reduce Thermal Sensitivity by Quantitative Sensory Testing to Below Pre-treatment Levels	6 months	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.

Secondary

Measure	Time frame	Description
Health-associated Quality of Life	6 months	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.
Number of Days With Pain Measured by iPad Daily Report Pain Calendar	8 months	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.
Changes in Individual Thermal Sensitivity Thresholds by QST	8 months	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.

Other

Measure	Time frame	Description
Fetal Hemoglobin (%)	6 months	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.
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)	6 months	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.
Plasma Endothelin-1(pg/ml)	6 months	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.
Thrombin Generation as Assessed by Calibrated Automated Thrombogram	6 months	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.
Plasma Levels of Soluble P-selectin (ng/ml)	6 months	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.
Plasma Levels of Soluble L-selectin (ng/ml)	6 months	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.
Hemostatic Markers in Plasma Including D-dimers and Prothrombin Fragment 1.2 (Nmol/L)	6 months	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.
Plasma Levels Soluble Vascular Adhesion Molecule -1 (VCAM-1) (ng/ml)	6 months	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.
High Sensitivity C-reactive Protein (mg/L)	6 months	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.
Plasma Lipidomic Analysis	6 months	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.
Urine Resolvin D1 (pg/mg Creatinine)	6 months	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.
Plasma Levels of Lactate Dehydrogenase (IU/L)	6 months	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
SCD-Omegatex™ single arm 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.	4
Total	4

Arm

Count

SCD-Omegatex™

single arm 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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	did not meet inclusion criteria	1
Overall Study	study terminated early	3

Baseline characteristics

Characteristic	SCD-Omegatex™
Age, Categorical <=18 years	2 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	2 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	4 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment United States	4 participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 3
other Total, other adverse events	1 / 4
serious Total, serious adverse events	1 / 3