Testing the safety of Avenanthramide in healthy individuals

A Double-Blind, Placebo-Controlled, Randomized, Adaptive, First-in-Human Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of Avenanthramide

This study is testing if a natural compound from oats called Avenanthramide is safe for healthy people and if it can help reduce inflammation in the body.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Montreal Heart Institute (other)
• Locations: 1 site (Montréal, Quebec)
• Trial ID: NCT06101784 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and tolerability of Avenanthramide, a natural compound derived from oats, through single and multiple ascending oral doses in healthy subjects. The study aims to understand the anti-inflammatory effects of Avenanthramide by monitoring biomarkers of inflammation in the blood. Participants will be required to avoid certain activities and dietary restrictions during the trial to ensure accurate results. The study is placebo-controlled to compare the effects of the compound against a non-active treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy males and females aged 18-60 with a BMI between 18.5 and 30.0.

Not a fit: Patients with significant underlying health conditions or those who consume oats or cannabis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new anti-inflammatory treatments derived from natural products for various inflammatory conditions.

How similar studies have performed: Other studies have shown promise with polyphenols in reducing inflammation, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

* 1. Male or female subjects;
* 2. Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively, for subjects participating in Part A and Part B;
* 3. Age 18-60 years;
* 4. Willing to avoid rigorous physical activity 1 day prior to the first drug administration and during study participation;
* 5. Willing to avoid oat consumption for 1 week prior to the first drug administration and during study participation;
* 6. Non- or ex-smoker; an ex-smoker is defined as someone who completely stopped using nicotine products for at least 6 months prior to the first study drug administration;
* 7. Non- or ex-consumer of cannabis; an ex-consumer of cannabis is defined as someone who stopped using cannabis derived products for at least 6 months prior to the first study drug administration;
* 8. Have no clinically significant diseases captured in the medical history and no evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by the investigator;
* 9. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without clinical significance, as determined by the investigator;
* 10. Provision of signed and dated informed consent form (ICF);
* 11. Stated willingness to comply with all study procedures and availability for the duration of the study;
* 12. A male subject meeting one of the following criteria:

  1. Subject is able to procreate and agrees to use one of the accepted contraceptive regimens and not donate sperm from the first study drug administration to at least 90 days after the last drug administration. An acceptable method of contraception includes one of the following:

     * True abstinence from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject (not periodic abstinence)
     * Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository) If the subject has a partner of childbearing potential, he and/or his partner must agree to use two acceptable birth control methods.

     Or
  2. Subject is unable to procreate; defined as surgically sterile (i.e., has undergone a vasectomy at least 6 months prior to the first study drug administration)
* 13. A female subject meeting one of the following criteria:

  1. Subject of childbearing potential must agree to use an effective double method of birth control from the first study drug administration to at least 30 days after the last drug administration: barrier method (e.g., male or female condoms, spermicides, sponges, foams, jellies, and diaphragm) in combination with other methods of contraception including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices; or must have a sterile sexual partner.

     Or
  2. Subject is of childbearing potential and agrees to abide by true abstinence from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject (not periodic abstinence) Or
  3. Subject is of non-childbearing potential, defined as surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a menopausal state (i.e., at least 1 year without menses prior to the first study drug administration).
* Part-C:

Inclusion Criteria modified:

In addition to the above criteria, the inclusion criterion #2 is defined as following:

2\*. Body mass index (BMI) within 18.5 kg/m2 to 34.0 kg/m2, inclusively, for the subjects participating in Part C.

Also, subjects with elevated waist circumference and low-grade inflammation must meet the following criteria in order to be included in the study:

* Waist circumference ≥ 100 cm in men and ≥ 85 cm in women
* Hs-CRP equal or greater than 2.0 mg/L and less than 10.0 mg/L at Screening

Exclusion Criteria:

* 1. Allergy to any ingredient of the Investigational Products, including excipients;
* 2. Oat products consumption within 1-week prior the first drug administration;
* 3. History of significant hypersensitivity to any excipients of the formulation, as well as severe hypersensitivity reactions (like angioedema) to any drug;
* 4. Presence of significant gastrointestinal (GI) conditions that interfere with absorption;
* 5. Presence of significant cardiovascular disease, gastrointestinal disease, kidney disease, or endocrine disease: including diabetes, and untreated thyroid disease, or rheumatoid arthritis;
* 6. Diagnosis of Gilbert syndrome;
* 7. Systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 95 mmHg at screening;
* 8. Major trauma or surgery within 3 months of study participation;
* 9. Presence of clinically significant ECG abnormalities at the screening, as defined by medical judgment;
* 10. Any clinically significant illness in the 28 days prior to the first study drug administration;
* 11. Any history of tuberculosis or proven contact with tuberculosis;
* 12. Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration;
* 13. Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HbsAg (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests at screening;
* 14. Active treatment for any type of cancer, except basal cell carcinoma, within 1 year prior to the first drug administration;
* 15. Use of any prescription drugs (with the exception of contraceptive or hormone replacement therapy) in the 28 days prior to the first study drug administration;
* 16. Regular use of anti-inflammatory drugs such as NSAIDs or aspirin in the 28 days prior to the first study drug administration;
* 17. Rigorous physical activity the day prior the first drug administration;
* 18. Nicotine smoking and/or nicotine replacement use;
* 19. Drinking alcohol \>10 drinks/week, or history of drug abuse;
* 20. Strict dietary restrictions (such as ketogenic or vegan diet);
* 21. Regular use of nutraceuticals such as resveratrol, immune boosters, glucosamine, chondroitin, Coenzyme Q10 supplementation in the 28 days prior to the first study drug administration;
* 22. Regular use of plant concentrates (including garlic, gingko, St. John's wort) homeopathic remedies, probiotics, or fish oil (including cod liver oil), in the 28 days prior to the first drug administration;
* 23. Females who are lactating or are pregnant according to the pregnancy test at screening or prior to the first study drug administration;
* 24. Subjects who have already been included in a previous group/cohort for this clinical study;
* 25. Subjects who took an Investigational Product (IP) in the 28 days prior to the first study drug administration;
* 26. Subjects who donated 50 mL and up to 450 mL of blood in the 28 days prior to the first study drug administration;
* 27. Donation of 450 mL or more of blood (Canadian Blood Services, Hema Quebec, clinical studies, etc.) in the 2 months prior to the first study drug administration for males, and in the 3 months prior to the first drug administration for females.

Where this trial is running

Montréal, Quebec

• Montreal Heart Institute — Montréal, Quebec, Canada (RECRUITING)

Study contacts

• Principal investigator: Jean-Claude Tardif, MD — Montreal Heart Institute
• Study coordinator: Jean-Claude Tardif, MD

Conditions: Inflammation, Healthy subjects, Single ascending dose, Multiple ascending dose, Natural product, Placebo controlled, First in human