Omega-3 Fatty Acids for Sickle Cell Disease

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Alabama at Birmingham

Must not be taking: Antibiotics, Prebiotics, Probiotics, PPIs

Disqualifiers: Chronic transfusion, Pregnancy, Breastfeeding, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a diet with plant-based omega-3 fatty acids to see if it helps children aged 5-18 with sickle cell disease by reducing their pain and inflammation.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are currently using antibiotics, pre or probiotic supplements, or PPI therapy (medications that reduce stomach acid).

What evidence supports the effectiveness of the treatment Omega-3 Fatty Acids for Sickle Cell Disease?

Research shows that omega-3 fatty acids, particularly DHA and EPA, can reduce inflammation and improve blood cell health in sickle cell disease. Studies have demonstrated that these fatty acids can lower the rate of sickle cell crises, improve blood flow, and reduce pain, making them a potentially effective treatment for managing sickle cell disease. ^{1 2 3 4 5}

Is it safe to use omega-3 fatty acids for sickle cell disease?

Research shows that omega-3 fatty acids, including DHA and EPA, are generally safe for people with sickle cell disease. They do not increase oxidative stress or worsen the condition, and they may even provide antioxidant protection and reduce inflammation. ^{1 2 3 4 5}

How is the treatment with plant-based omega-3 fatty acids for sickle cell disease different from other treatments?

This treatment is unique because it uses plant-based omega-3 fatty acids, like alpha-linolenic acid (ALA), which can be converted in the body to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), offering a sustainable alternative to marine sources. Unlike traditional treatments, it focuses on dietary supplementation to potentially improve health outcomes in sickle cell disease. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

This trial is for children and teenagers aged 5-18 with sickle cell anemia (HbSS or HbSB0 thal) who are not on chronic transfusion therapy, not taking pre/probiotic supplements, antibiotics, PPIs, and aren't pregnant or breastfeeding. They should also have no known allergy to plant-based omega-3 fatty acids.

Inclusion Criteria

I am between 5 and 18 years old.

I have been diagnosed with sickle cell anemia.

Exclusion Criteria

Use of pre or probiotic supplements

I am older than 18 years.

I am currently taking proton pump inhibitors.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive a diet rich in omega-3-fatty acids versus a regular diet for 12 weeks

12 weeks

Weekly pain diaries and acute care visits for pain

Washout

A 4-week washout period before crossover of arms

4 weeks

Crossover Treatment

Participants switch to the alternate diet for another 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Plant-based omega-3-FA (Omega-3 Fatty Acids)

Trial Overview The study tests if plant-based omega-3 fatty acids can be a more acceptable treatment option for SCD patients and improve their outcomes by reducing inflammation-related pain compared to fish oil-derived omega-3s.

Participant Groups

Group I: Plant based omega 3 Fatty Acid Experimental Treatment 1 Intervention

Participants ingest their regular diet supplemented with a plant-based omega-3-FA

Group II: Regular diet Active Control 1 Intervention

Participants will continue their regular diet.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

Supplementation with omega-3 fatty acids (n-3) in sickle cell disease (SCD) patients led to increased levels of beneficial fatty acids (DHA and EPA) and reduced white blood cell counts, indicating a potential anti-inflammatory effect.

The n-3 treated group showed lower expression of the NF-κB gene, which is associated with inflammation, suggesting that omega-3 fatty acids may help reduce inflammation and blood cell adhesion in SCD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega 3 (n-3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease. Daak, AA., Elderdery, AY., Elbashir, LM., et al.[2022]

Omega-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation in sickle cell patients aged 2 to 14 years significantly increased levels of beneficial fatty acids in red blood cells and plasma vitamin E, suggesting a positive impact on antioxidant status.

The study found that omega-3 supplementation reduced oxidative stress markers (GPx-1 and Cu/Zn-SOD activities) compared to placebo, indicating that omega-3 LCPUFA may provide antioxidant protection rather than worsening oxidative stress in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docosahexaenoic and eicosapentaenoic acid supplementation does not exacerbate oxidative stress or intravascular haemolysis in homozygous sickle cell patients. Daak, AA., Ghebremeskel, K., Mariniello, K., et al.[2022]

In the SCOT trial involving 67 children with sickle cell disease, treatment with the novel DHA formulation SC411 significantly increased blood cell membrane levels of DHA and eicosapentaenoic acid, indicating enhanced bioavailability of DHA.

SC411 treatment led to a reduction in sickle cell crises, analgesic use, and school absences due to pain, with all doses being safe and well tolerated, although the reduction in crisis rate did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial). Daak, AA., Dampier, CD., Fuh, B., et al.[2021]

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), show promise as a safe and effective treatment for sickle cell disease (SCD) by improving inflammation and hemolysis, as evidenced by clinical studies.

Treatment with DHA has been linked to better rheological properties of sickle red blood cells and reductions in vaso-occlusive crisis rates, inflammation markers, and hemolysis, suggesting a beneficial impact on the disease's complex pathophysiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical and therapeutic effects of Omega-3 fatty acids in sickle cell disease. Daak, AA., Lopez-Toledano, MA., Heeney, MM.[2021]

A study involving 30 children with sickle cell disease found that flaxseed, a plant-based source of omega-3 fatty acids, was well-accepted when added to baked goods and other foods, with brownies and cookies being the most favored.

Over 80% of participants expressed interest in participating in a follow-up study to evaluate the effects of a flaxseed-supplemented diet on pain associated with sickle cell disease, indicating potential for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palatability and Acceptability of Flaxseed-Supplemented Foods in Children with Sickle Cell Disease. Dike, CR., Lebensburger, J., Mitchell, C., et al.[2023]

Camelina oil, which is high in ALA, significantly increased levels of DPA and DHA in the blood of rats, indicating effective conversion of ALA to these important fatty acids.

Sandeel oil, rich in cetoleic acid, can be combined with camelina oil without negatively affecting the levels of EPA, DPA, or DHA, suggesting that cetoleic acid may enhance the conversion process and counteract the inhibition of the n-3 biosynthetic pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different Dietary Ratios of Camelina Oil to Sandeel Oil Influence the Capacity to Synthesise and Deposit EPA and DHA in Zucker Fa/Fa Rats. Østbye, TK., Gudbrandsen, OA., Drotningsvik, A., et al.[2023]

Very long chain omega-3 fatty acids, specifically EPA and DHA, are linked to significant cardiovascular and mental health benefits, highlighting their importance in human nutrition.

Recent advancements allow for the engineering of common oilseed crops like soybean and canola to produce EPA and DHA, potentially providing a more desirable and sustainable source of these beneficial fatty acids compared to traditional fish oils.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering oilseed plants for a sustainable, land-based source of long chain polyunsaturated fatty acids. Damude, HG., Kinney, AJ.[2018]

Supplementing dogs' diets with stearidonic acid (SDA) significantly increased the levels of eicosapentaenoic acid (EPA) in red blood cells and heart tissue in a dose-dependent manner, indicating its potential as a plant-based source of omega-3 fatty acids.

While SDA was effective in raising EPA levels, it was only 20-23% as efficient as direct EPA supplementation, suggesting that while SDA can be beneficial, it may not fully replace the need for direct sources of EPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stearidonic acid increases the red blood cell and heart eicosapentaenoic acid content in dogs. Harris, WS., DiRienzo, MA., Sands, SA., et al.[2018]

Omega-3 polyunsaturated fatty acids, particularly ALA, EPA, and DHA, are crucial for organ development and maintenance, especially in the brain, and may help prevent various diseases, including cardiovascular and psychiatric disorders.

Feeding animals diets enriched with omega-3 sources like linseed and rapeseed can significantly increase the omega-3 content in their products, such as eggs and fish, enhancing their nutritional value for human consumption, with the most substantial effects seen in eggs and fish compared to beef.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of increasing the omega-3 fatty acid in the diets of animals on the animal products consumed by humans]. Bourre, JM.[2008]

For the first time, researchers successfully engineered Arabidopsis thaliana to produce docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in seed oils, which are important omega-3 fatty acids typically sourced from marine life.

The study showed that using specific enzymes for fatty acid synthesis in plants resulted in higher levels of these beneficial fatty acids than previous methods, highlighting the potential of land plants as sustainable sources of DHA and other long-chain polyunsaturated fatty acids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic engineering of Arabidopsis to produce nutritionally important DHA in seed oil. Robert, SS., Singh, SP., Zhou, XR., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Omega 3 (n-3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease. [2022]

2. Scotland pubmed.ncbi.nlm.nih.gov

Docosahexaenoic and eicosapentaenoic acid supplementation does not exacerbate oxidative stress or intravascular haemolysis in homozygous sickle cell patients. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial). [2021]

4. Scotland pubmed.ncbi.nlm.nih.gov

Biochemical and therapeutic effects of Omega-3 fatty acids in sickle cell disease. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Palatability and Acceptability of Flaxseed-Supplemented Foods in Children with Sickle Cell Disease. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Different Dietary Ratios of Camelina Oil to Sandeel Oil Influence the Capacity to Synthesise and Deposit EPA and DHA in Zucker Fa/Fa Rats. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Engineering oilseed plants for a sustainable, land-based source of long chain polyunsaturated fatty acids. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Stearidonic acid increases the red blood cell and heart eicosapentaenoic acid content in dogs. [2018]

9. France pubmed.ncbi.nlm.nih.gov

[Effect of increasing the omega-3 fatty acid in the diets of animals on the animal products consumed by humans]. [2008]

10. Australia pubmed.ncbi.nlm.nih.gov

Metabolic engineering of Arabidopsis to produce nutritionally important DHA in seed oil. [2020]