Omega-3 Fatty Acids for Sickle Cell Disease

Overseen By Dike

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

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

Disqualifiers: Chronic transfusion, Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether plant-based omega-3 fatty acids can reduce pain and improve outcomes for people with sickle cell disease. Sickle cell disease often causes painful episodes and complications linked to inflammation, and omega-3s might help combat this inflammation. The study compares a regular diet to one that includes these plant-based supplements. Children with sickle cell anemia, who are not on antibiotics or probiotic supplements and are between 5 and 18 years old, might be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to understanding how dietary changes might improve health outcomes for sickle cell patients.

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).

Is there any evidence suggesting that plant-based omega-3 fatty acids are safe for individuals with sickle cell disease?

Research has shown that omega-3 fatty acids, such as those in fish oil, are generally safe for individuals with sickle cell disease. They do not increase oxidative stress, meaning they don't cause additional cell damage. Omega-3s have been studied for their anti-inflammatory effects, which help reduce swelling and pain, offering benefits in managing sickle cell disease.

This research focuses on plant-based omega-3s, expected to be as safe as those from fish. They should be well-tolerated and not cause major side effects, making them a promising option for those seeking to improve their condition safely. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for sickle cell disease, which often include pain management, blood transfusions, and hydroxyurea, this new treatment uses plant-based omega-3 fatty acids. Researchers are excited about it because omega-3 fatty acids have anti-inflammatory properties that could help reduce the painful episodes and complications associated with sickle cell disease. Additionally, being plant-based, this treatment might offer a more natural and potentially safer alternative with fewer side effects compared to traditional medications. This novel approach offers hope for improved quality of life for those living with the condition.

What evidence suggests that plant-based omega-3 fatty acids might be an effective treatment for sickle cell disease?

Research has shown that omega-3 fatty acids, especially DHA and EPA, can reduce inflammation and improve blood cell health in people with sickle cell disease (SCD). These fatty acids are often low in the blood cells of those with SCD. Omega-3s possess anti-inflammatory properties, which is crucial because inflammation can worsen SCD symptoms. While fish oil is a common source, this trial will examine plant-based omega-3s from sources like perilla seed and sea buckthorn. Participants will either continue their regular diet or supplement it with plant-based omega-3 fatty acids, which might be a more acceptable option for some, potentially improving outcomes for those with SCD. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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 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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Plant-based omega-3-FA

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.

How Is the Trial Designed?

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.

Plant-based omega-3-FA is already approved in United States, European Union for the following indications:

Approved in United States as Plant-based omega-3 fatty acids for:

• Sickle Cell Disease

Approved in European Union as Plant-based omega-3 fatty acids for:

• Sickle Cell Disease

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. rarediseaseadvisor.com rarediseaseadvisor.com/news/new-study-assess-plant-based-omega-3-fatty-acids-outcomes-scd/

New Study to Assess Plant-Based Omega-3 Fatty Acids in ... A new study is set to assess the use of plant-based omega-3 fatty acids for better acceptability and outcomes in SCD.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2097382924000337

Omega-3 in traditional medicine and its role in the ... Omega-3 has been shown to alleviate SCD and has been found to be richly available in traditional medicinal plants such as perilla seed, sea buckthorn and ...

3. withpower.com withpower.com/trial/phase-anemia-sickle-cell-3-2023-0a195

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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6681670/

Relationship of Omega-3 Fatty Acids DHA and EPA with ... Findings demonstrate relative deficiencies in HbSS of the anti-inflammatory precursor fatty acids DHA and EPA, which correlates positively with hs-CRP.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0965229920302879

Biochemical and therapeutic effects of Omega-3 fatty acids ... Omega-3 fatty acids have anti-inflammatory properties. Sickle cell disease blood cell membranes have low omega-3 fatty acid composition.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37121179/

An open-label, multicenter, phase 2 study of a food ... We investigated a food enriched with omega-3 fatty acids to determine its effect on certain factors: blood cell membrane fatty acid composition.