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Sickle Cell Omega-3 Treatment Trial (SCOT Trial) (SCOT)

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified November 2016 by Sancilio and Company, Inc.
Sponsor:
Information provided by (Responsible Party):
Sancilio and Company, Inc.
ClinicalTrials.gov Identifier:
NCT02604368
First received: November 11, 2015
Last updated: November 22, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to determine whether treatment of sickle cell patients with docosahexaenoic omega-3 acid (DHA) is effective in prevention of acute sickle cell crisis.

Condition Intervention Phase
Sickle Cell Disease Drug: SC411 Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Prospective, Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multi-center Study of SC411 for Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Sancilio and Company, Inc.:

Primary Outcome Measures:
  • Annualized sickle cell crisis rate [ Time Frame: 52 weeks ]
    The total number of adjudicated acute sickle cell crises divided by the total number of months in the study from randomization then multiplied by 12


Secondary Outcome Measures:
  • Annualized rate of diary-recorded painful crises [ Time Frame: 52 weeks ]
  • Annualized rate of emergency room/medical facility visits [ Time Frame: 52 weeks ]
  • Annualized rate of hospitalizations for sickle cell crises [ Time Frame: 52 weeks ]
  • Cumulative number of hospitalization days for sickle cell crises [ Time Frame: 52 weeks ]
  • Cumulative number of days out of school (ie, absence) due to SCD [ Time Frame: 52 weeks ]

Other Outcome Measures:
  • Intensity of diary-recorded painful crises [ Time Frame: 52 weeks ]
  • Frequency of analgesic use at home [ Time Frame: 52 weeks ]
  • Time to first and second sickle cell disease crisis [ Time Frame: 52 weeks ]
  • Hemoglobin concentration (g/L) [ Time Frame: 52 weeks ]
  • Hematocrit (%) [ Time Frame: 52 weeks ]
  • Total white blood cell count ( X1000/µL) [ Time Frame: 52 ]
  • Platelet Count (X1000/µL) [ Time Frame: 52 weeks ]
  • reticulocyte count (X1000/µL) [ Time Frame: 52 weeks ]
  • Plasma levels of Lactate dehydrogenase (IU/L) [ Time Frame: 52 weeks ]
  • High sensitive C-reactive protein (mg/L) [ Time Frame: 52 ]
  • Indirect bilirubin (mg/dL) [ Time Frame: 52 weeks ]
  • Plasma levels of D-dimer [ng/mL] [ Time Frame: 52 weeks ]
    marker of coagulation

  • Plasma levels of thrombin-antithrombin complex [nmol/L] [ Time Frame: 52 weeks ]
    marker of coagulation

  • Plasma levels of microparticle-associated tissue factor [MP-TF] [fmol/L] [ Time Frame: 52 weeks ]
    marker of coagulation

  • Plasma levels of soluble vascular cell adhesion molecule [sVCAM] [ mg/mL], [ Time Frame: 52 weeks ]
    Biomarker of endothelial activation

  • Plasma levels of soluble E-selectin [sE-sel] [mg/mL] [ Time Frame: 52 weeks ]
    Biomarker of endothelial activation

  • Plasma levels of Soluble P-selectin [sP-sel] [mg/mL]) [ Time Frame: 52 weeks ]
    Biomarker of endothelial activation


Estimated Enrollment: 213
Study Start Date: July 2017
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SC411
Omega-3 docosahexaenoic acid, soft gelatin capsule, once a day
Drug: SC411
Soft gelatin capsule
Other Name: Docosahexaenoic acid (DHA)
Placebo Comparator: Placebo
Soybean oil, soft gelatin capsule
Drug: Placebo
Soft gelatin capsule
Other Name: Soybean Oil

Detailed Description:

Sickle cell disease (SCD) is an inherited blood disease that affects millions of people worldwide and about 100,000 Americans. Sickle cell disease is a group of blood disorders that affect hemoglobin (Hb), the molecule that delivers oxygen throughout the body via red blood cells. The abnormal sickle cell Hb polymerizes under low oxygen tension and causes RBCs to become distorted into a rigid sickle, or crescent shape. Sickle cells have a shorter lifespan than normal RBCs. As a result, patients with SCD frequently develop anemia, leading to fatigue, weakness, shortness of breath, dizziness, headaches, and coldness in the hands and feet. In children with SCD, anemia can also cause delayed growth and development.

Sickle red blood cells are also prone to adhesive interactions with each other, white blood cells, platelets, and blood vessel walls. These adhesive interactions lead to occlusion of the small blood vessels, blocking the flow of blood, and cause inflammation and multiple organ damage. Acute blockage of the blood vessels results in episodic events that are known as sickle cell crises, and they are accompanied by 3 serious symptoms: pain, organ damage and inflammation.

Pharmacotherapy of SCD is limited to hydroxyurea, the only FDA approved drug for the treatment of sickle cell disease. However, considerable percentage of patients with sickle disease are not responsive or showing varying degree of response to hydroxyurea treatment.

For a very long time, the investigators understanding of the underlining pathological processes which lead to the occlusion of the blood vessel was dominated by the simplistic mechanical approach. However, the emerging evidence indicates that primary events in vaso-occlusion are triggered by polymerization-independent events, with sickling occurring as secondary incident. The current consensus is that, the primary events crucial to vaso-occlusion are due to inflammation and increased adhesion of RBC, platelet and leukocyte to blood vessels lining tissue (endothelium). This new paradigm of pathophysiology of the disease has shifted the management strategies from prevention of Hb polymerization to amelioration of the inflammation and reduction of blood cell adhesion. In order to elucidate the changes behind the increased propensity of blood cells to adhere to each other and the endothelium extensive studies were conducted on red blood cell membrane. The major membrane abnormalities observed in red blood cell of SCD patients compromise membrane transport defects, dysfunctional lipid bilayer and perturbation of fatty acid composition of membrane phospholipids. The abnormality is characterized by high omega-6, low omega-3 and an imbalance between the two fatty acid families. The fatty acid imbalance in SCD is known contributory factor in enhanced blood cell adhesion, aggregation, blood coagulation and inflammation (Daak et al 2013; Daak et al 2015).

SC411 is a drug based on omega-3 docosahexaenoic acid (DHA) that may help prevent sickle cell crises, decrease inflammation and continuous breakdown of red blood cells. The active ingredient DHA, is formulated using advanced Lipid Technologies™ (ALT™), and encapsulated in a soft gelatin capsule. In this study investigator will compare the rate of sickle cell crises between individuals with sickle cell anemia disease receiving SC411 capsules vs. placebo capsules. The results of this research will provide the evidence about the potential therapeutic effect of SC411 in SCD.

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients who meet all of the following criteria will be eligible to participate in the study:

  1. Aged ≥ 5 years and ≤17 years at screening;
  2. Has been diagnosed with SCD (that includes the genotypes HbSS, HbSC, and HbS/beta thalassemia documented by hemoglobin HPLC or electrophoresis);
  3. Has had between ≥ 2 to ≤ 10 episodes of clinical sickle cell crises within 12 months of the Screening Visit.
  4. Is either not on hydroxyurea at the Screening Visit and does not plan on receiving it during the course of the study or has received hydroxyurea for a minimum of 12 months and is dose stabilized for at least 6 months prior to the Screening Visit with the intent to continue for the duration of the study;
  5. Parent or guardian is able to give written informed consent, and the potential pediatric patient is able to provide assent in a manner approved by the Institutional Review Board (IRB) and comply with the requirements of the study; and
  6. If sexually active, agrees to use a reliable method of birth control (eg, barrier, birth control pills, abstinence) during the study and for 1 month following the last dose of study drug.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from participation in the study:

  1. Has a significant medical condition that required hospitalization (other than sickle cell crisis) within 2 months of the Screening Visit;
  2. Has chronic daily use of opioid analgesia for any reason;
  3. Has a diagnosis of chronic pain or chronic pain syndrome (eg, chronic pain from the repeated vaso-occlusive events, chronic pain from avascular necrosis);
  4. Has a history of Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection;
  5. Has a history of documented episode(s) of priapism within 12 months of the Screening Visit;
  6. Has international normalized ratio (INR) >2.0 or is on regular anticoagulation;
  7. Has thrombocytopenia (platelets < 80,000) or is on chronic ASA therapy;
  8. Has increased risk of stroke: documented abnormal or "high conditional" transcranial Doppler (TCD) mean velocity (TCD V) by STOP criteria (Adams, 1998) within the preceding year or has a history of moyamoya syndrome:

    1. "High conditional" = TCD V ≥ 185-199 cm/sec, or TCDi V ≥170-184 cm/sec, or TCD maximum V ≥250 cm/sec;
    2. Abnormal = TCD V≥ 200 cm/sec, or abnormal high TCDi V≥ 185 cm/sec, or TCD maximum V≥ 250 cm/sec;
  9. Has received a blood transfusion in the 2 months prior to the Screening Visit or 3 months prior to randomization or has hemoglobin A (HbA) levels >15% at the Screening Visit;
  10. Has received any blood products in the 2 months prior to the Screening Visit or 3 months prior to randomization;
  11. Has renal insufficiency (creatinine >1.5 x ULN, or requiring peritoneal or hemodialysis);
  12. Has liver dysfunction (ALT >2.0 x ULN);
  13. Has other concomitant chronic medical or psychiatric condition that in the opinion of the Investigator would compromise participation in the study or confound the evaluation of the study outcome;
  14. Is pregnant or lactating or has the intention of becoming pregnant during the study (if a female of child-bearing potential or partner of a patient participating in the study);
  15. Is currently taking or has been treated with any form of omega-3 fatty acid or fish oil supplement within 30 days of the Screening Visit or during the course of the study;
  16. Has been treated with an experimental anti-sickling medication/treatment within 30 days of the Screening Visit or during the course of the study;
  17. Is currently taking or has been treated with any investigational drug for any disease within 30 days of the Screening Visit or during the course of the study;
  18. Is currently enrolled in an investigational drug or device study and/or has participated in such a study within 30 days of the Screening Visit or during the course of the study; or
  19. There are factors that would, in the judgment of the Investigator, make it difficult for the patient to comply with the requirements of the study (eg, inability to swallow capsules due to past history of stroke).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02604368

Contacts
Contact: Heeney Matthew, MD 6179193242 Matthew.Heeney@childrens.harvard.edu
Contact: Ahmed A Daak, MB BS, PhD 5618472302 adaak@sancilio.com

Sponsors and Collaborators
Sancilio and Company, Inc.
Investigators
Study Director: Ahmed A Daak, MB BS,PhD Sancilio& Company, Inc
  More Information

Additional Information:
Publications:
Responsible Party: Sancilio and Company, Inc.
ClinicalTrials.gov Identifier: NCT02604368     History of Changes
Other Study ID Numbers: OMEG-411-01
Study First Received: November 11, 2015
Last Updated: November 22, 2016

Keywords provided by Sancilio and Company, Inc.:
hemoglobin SS
hemoglobin SC
hemoglobin S/β°-thalassemia

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 21, 2017