Omega-3 Fatty Acids in Sickle Cell Disease

• Sponsor: Robin E. Miller (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02947100
• Collaborator: National Institute of General Medical Sciences (NIGMS) (NIH), Thomas Jefferson University (Other), Solutex GC, S.L. (Other)
• Enrollment: 4
• Location: 1
• Arm: 1
• Actual Duration (Months): 8.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: SCD-Omegatex™	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Jan 25, 2018
• Actual Primary Completion Date: Oct 5, 2018
• Actual Study Completion Date: Oct 15, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: SCD-Omegatex™ single arm

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.; Other Names: Enteric Fish Oil 250 DHA/27 EPA Soft Gelatin Capsule

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nemours/Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19899

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Robin E Miller, MD, Nemours Children's Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 18, 2018

More Information

Publications

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

• Responsible Party: Robin E. Miller, Physician, Nemours Children's Clinic
• ClinicalTrials.gov Identifier: NCT02947100
• Other Study ID Numbers: RM002; P20GM109021
• First Posted: Oct 27, 2016
• Last Update Posted: Oct 19, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Robin E. Miller, Physician, Nemours Children's Clinic: Sickle Cell Disease; omega-3 fatty acids; Docosahexaenoic Acid (DHA); Eicosapentaenoic Acid (EPA)
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

Participant Flow

Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
Period Title: Overall Study
STARTED	4
COMPLETED	0
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
Overall Participants	4
Age (Count of Participants)
<=18 years	2 50%
Between 18 and 65 years	2 50%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	3 75%
Male	1 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	4 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 100%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Safety, in a Dose Escalation Trial of SCD-Omegatex™ as Evidenced by an Absence of Adverse Events.
Description	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.
Time Frame	6 months with continuous monitoring

Outcome Measure Data

Analysis Population Description

Study was stopped early, before outcomes could be measured, due to manufacturing issues with the study drug

Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
Measure Participants	0

2. Primary Outcome

Title	Determine Whether 6 Months of Supplementation With SCD-Omegatex™ Will Reduce Thermal Sensitivity by Quantitative Sensory Testing to Below Pre-treatment Levels
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Study was stopped early, before outcomes could be measured, due to manufacturing issues with the study drug

Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
Measure Participants	0

3. Secondary Outcome

Title	Health-associated Quality of Life
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Study was stopped early, before outcomes could be measured, due to manufacturing issues with the study drug

Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
Measure Participants	0

4. Secondary Outcome

Title	Number of Days With Pain Measured by iPad Daily Report Pain Calendar
Description	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.
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Study was stopped early, before outcomes could be measured, due to manufacturing issues with the study drug

Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
Measure Participants	0

5. Secondary Outcome

Title	Changes in Individual Thermal Sensitivity Thresholds by QST
Description	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.
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Study was stopped early, before outcomes could be measured, due to manufacturing issues with the study drug

Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
Measure Participants	0

6. Other Pre-specified Outcome

Title	Thrombin Generation as Assessed by Calibrated Automated Thrombogram
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	High Sensitivity C-reactive Protein (mg/L)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Plasma Lipidomic Analysis
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Urine Resolvin D1 (pg/mg Creatinine)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Plasma Levels of Lactate Dehydrogenase (IU/L)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Fetal Hemoglobin (%)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	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)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Plasma Endothelin-1(pg/ml)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	Plasma Levels Soluble Vascular Adhesion Molecule -1 (VCAM-1) (ng/ml)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Other Pre-specified Outcome

Title	Plasma Levels of Soluble P-selectin (ng/ml)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Other Pre-specified Outcome

Title	Plasma Levels of Soluble L-selectin (ng/ml)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Other Pre-specified Outcome

Title	Hemostatic Markers in Plasma Including D-dimers and Prothrombin Fragment 1.2 (Nmol/L)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Until one month after stopping study drug
Arm/Group Title	SCD-Omegatex™
Arm/Group Description	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.
All Cause Mortality
	SCD-Omegatex™
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Serious Adverse Events
	SCD-Omegatex™
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Reproductive system and breast disorders
Mondor's disease	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	SCD-Omegatex™
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Blood and lymphatic system disorders
nosebleed	1/3 (33.3%)	1
Eye disorders
stye	1/3 (33.3%)	1
Gastrointestinal disorders
constipation	1/3 (33.3%)	1
nausea	1/3 (33.3%)	1
General disorders
fever	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
vasoocclusive crisis	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
rash	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.