Avenanthramide for Inflammation

(AvenActive Trial)

Recruiting at 1 trial location

Overseen By Marianne Rufiange, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Montreal Heart Institute

Must not be taking: NSAIDs, Aspirin, others

Disqualifiers: Cardiovascular, Diabetes, Hypertension, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and tolerability of avenanthramide, a compound found in oats. Researchers are interested in its potential to reduce inflammation, often linked to conditions like asthma or arthritis. Participants will receive either a single or multiple doses of avenanthramide or a placebo to compare effects. Men with a waist circumference over 100 cm and women over 85 cm, along with signs of mild inflammation, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription drugs (except contraceptive or hormone replacement therapy) and regular use of anti-inflammatory drugs like NSAIDs or aspirin at least 28 days before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that avenanthramides, compounds found in oats, may help reduce inflammation by influencing certain genes related to it. Previous studies suggest that avenanthramides might lower the risk of diseases linked to inflammation, such as heart problems.

While interest in their health benefits exists, researchers are still studying the safety of avenanthramides in humans. This trial is in its early stages, so researchers are carefully monitoring participants' reactions to these compounds. Early trials mainly focus on safety and determining the right dose. Although avenanthramides are present in foods like oats, understanding their effects at higher doses is crucial for treatment safety.

In summary, avenanthramides have shown potential benefits in lab studies and are generally safe in food. However, this trial aims to confirm their safety and tolerance when used as a treatment. Participants will be closely monitored to address any side effects promptly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard anti-inflammatory treatments like NSAIDs and corticosteroids, Avenanthramide offers a novel approach by harnessing a naturally occurring compound found in oats. This active ingredient is thought to have antioxidant and anti-inflammatory properties, potentially offering a gentler option with fewer side effects. Researchers are excited because Avenanthramide could provide effective relief with adaptive dosing, allowing for tailored treatment that aligns more closely with individual patient needs.

What evidence suggests that avenanthramide might be an effective treatment for inflammation?

Research has shown that avenanthramides, compounds found in oats, may help reduce inflammation. Studies indicate that they can lower the activity of certain enzymes and proteins that cause inflammation, such as cyclo-oxygenase and cytokines, which are chemical messengers in the body. These compounds also affect cellular processes that control inflammation and might help reduce inflammation markers in the blood, like C-reactive protein. Early findings suggest that avenanthramides could decrease inflammation by altering these biological processes. While more research is needed, the evidence so far supports the potential of avenanthramides to help with inflammatory conditions. Participants in this trial will receive either a single or multiple oral doses of avenanthramide, or a placebo, to further evaluate its effects on inflammation. ^{1 4 5 6 7}

Who Is on the Research Team?

Jean-Claude Tardif, M.D

Principal Investigator

Montreal Heart Institute

Are You a Good Fit for This Trial?

Healthy adults or those with a larger waist and low-grade inflammation can join this trial. They must not smoke, use drugs, or have significant health issues. Women of childbearing age should use effective birth control, while men agree to contraception and no sperm donation for 90 days post-trial.

Inclusion Criteria

You agree to abstain from consuming oats for seven days before starting the medication and throughout the duration of the study.

You have no noted medical illness, physical abnormalities or concerning ECG readings.

My partner and I agree to use two forms of birth control if she can have children.

Exclusion Criteria

Subjects who took an Investigational Product (IP) in the 28 days prior to the first study drug administration

I have a stomach or intestine condition that affects how my body absorbs medicine.

I have not taken supplements like resveratrol or CoQ10 in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single and multiple ascending oral doses of avenanthramide to assess safety, tolerability, and pharmacokinetics

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in vital signs, adverse events, and laboratory parameters

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Avenanthramide

Trial Overview The trial is testing Avenanthramide (AVA), a compound from oats thought to reduce inflammation. Participants will take either AVA or a placebo in single or multiple doses to check safety, tolerability, and how the body processes it.

How Is the Trial Designed?

Group I: Avenanthramide tablet single oral dose Active Control 1 Intervention

adaptive dose levels

Group II: Avenanthramide tablet multiple oral dose Active Control 1 Intervention

adaptive dose levels

Group III: Placebo to match Avenanthramide tablet single oral dose Placebo Group 1 Intervention

adaptive dose levels

Group IV: Placebo to match Avenanthramide tablet multiple oral dose Placebo Group 1 Intervention

adaptive dose levels

Avenanthramide is already approved in Canada for the following indications:

Approved in Canada as Avenanthramides for:

• Inflammation

Who Is Running the Clinical Trial?

Montreal Heart Institute

Lead Sponsor

Trials

125

Recruited

85,400+

The Montreal Health Innovations Coordinating Center (MHICC)

Collaborator

Trials

14

Recruited

10,900+

Ceapro Inc.

Collaborator

Trials

2

Recruited

360+

Ceapro Inc.

Industry Sponsor

Trials

2

Recruited

360+

Published Research Related to This Trial

Three new compounds derived from oat seeds were identified as amides of 4,5-dihydroxyanthranilic acid with caffeic, p-coumaric, and ferulic acids, showing potential as beneficial constituents of oats.

These compounds exhibited stronger antioxidant activity than traditional avenanthramides, suggesting that they may play a significant role in scavenging harmful free radicals, which could have health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New series of avenanthramides in oat seed. Ishihara, A., Kojima, K., Fujita, T., et al.[2021]

A new high-performance liquid chromatography (HPLC) method was developed to analyze avenanthramides in oats, revealing that these compounds can make up to 20% of the total avenanthramides detected in oat products.

The study found that avenanthramide content in oat products ranged from 2 to 82 µg/g, leading to an estimated daily intake of 0.3 to 2.1 mg for oat consumers, which is significantly lower than the amounts used in previous studies examining their biological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of avenanthramides in oat products and estimation of avenanthramide intake in humans. Pridal, AA., Böttger, W., Ross, AB.[2019]

Opuntia species, a type of cactus, contain various phenolic compounds like quercetin and kaempferol, which have demonstrated significant anti-inflammatory effects in both laboratory and animal studies.

These compounds may help modulate inflammation by affecting cell infiltration and the secretion of inflammatory mediators, supporting the traditional use of Opuntia in folk medicine for treating conditions like asthma and burns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenolic Compounds' Occurrence in Opuntia Species and Their Role in the Inflammatory Process: A Review. Zeghbib, W., Boudjouan, F., Vasconcelos, V., et al.[2022]

New dimers of avenanthramide B were discovered in oat leaves after pathogen attack, indicating a potential role in plant defense mechanisms.

These dimers were formed through a reaction involving peroxidase and hydrogen peroxide, suggesting a specific biochemical pathway for their synthesis that could enhance our understanding of plant responses to stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New dimeric compounds of avenanthramide phytoalexin in oats. Okazaki, Y., Ishizuka, A., Ishihara, A., et al.[2022]

Avenanthramides, compounds found in oats, have been shown to inhibit inflammation in skin cells at very low concentrations (as low as 1 part per billion), suggesting they play a key role in the soothing effects of oatmeal for skin irritation.

Topical application of avenanthramides significantly reduced inflammation and itching in mouse models, indicating their potential as effective anti-inflammatory agents for treating skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity. Sur, R., Nigam, A., Grote, D., et al.[2022]

Avenanthramide-C (2c), a compound found in oats, is extensively metabolized in mice and by human gut bacteria, producing eight metabolites that may have health benefits.

One of the major metabolites, dihydroavenanthramide-C (M6), shows greater anti-cancer activity against human colon cancer cells than 2c itself, indicating its potential as a bioactive compound.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oat avenanthramide-C (2c) is biotransformed by mice and the human microbiota into bioactive metabolites. Wang, P., Chen, H., Zhu, Y., et al.[2023]

This study identified and characterized seven A-type avenanthramides (AVAs) from sprouted oat bran, with five of these compounds being isolated for the first time, highlighting their potential as unique phytochemicals in oats.

The A-type AVAs demonstrated anti-inflammatory properties similar to C-type AVAs, suggesting that both types of AVAs could be beneficial in reducing inflammation, which is important for health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Analysis and Anti-inflammatory Activity Evaluation of the A-Type Avenanthramides in Commercial Sprouted Oat Products. Hu, C., Tang, Y., Zhao, Y., et al.[2021]

The hexane extract and lignan-rich fraction from Phyllanthus amarus showed significant anti-inflammatory effects by reducing paw swelling and neutrophil influx in a carrageenan-induced inflammation model.

Specific lignans, particularly niranthin, phyltetralin, and nirtetralin, were identified as the main active compounds responsible for these anti-inflammatory properties, suggesting their potential as therapeutic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory properties of extracts, fractions and lignans isolated from Phyllanthus amarus. Kassuya, CA., Leite, DF., de Melo, LV., et al.[2017]

Avenanthramides, antioxidants found in oats, showed no toxicity to human aortic endothelial cells (HAEC) at concentrations up to 40 ng/ml, indicating their safety for potential therapeutic use.

The avenanthramide-enriched mixture significantly reduced the adhesion of monocytes to endothelial cells and suppressed the expression of key adhesion molecules and proinflammatory cytokines, suggesting their potential role in preventing atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antiatherogenic potential of oat phenolic compounds. Liu, L., Zubik, L., Collins, FW., et al.[2022]

A series of novel acanthoic acid analogs were synthesized, demonstrating strong anti-inflammatory effects.

The study provides insights into the mechanisms by which these analogs exert their anti-inflammatory properties, highlighting their potential as therapeutic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and anti-inflammatory effects of novel pimarane diterpenoid analogs. Suh, YG., Lee, KO., Moon, SH., et al.[2019]

Total glycosides of Acanthopanax Giraldii (TGA) significantly reduce the production of inflammatory markers prostaglandin E(2) (PGE(2)) and nitric oxide (NO) in mouse macrophages, with an inhibitory rate of 87% for PGE(2) at 100 mg/L.

TGA inhibits the expression of COX-2 mRNA, which is a key enzyme in the inflammatory process, while not affecting TNF-alpha levels, indicating a specific anti-inflammatory mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory mechanism of total glycosides of Acanthopanax Giraldii. Yuan, F., Chen, J., Xu, GM., et al.[2021]

The methanol extract of Capparis ecuadorica leaves (MCE) significantly reduced inflammation in both LPS-stimulated RAW 264.7 cells and in a mouse model of atopic dermatitis, showing a decrease in key inflammatory markers and symptoms such as ear thickness and IgE concentration.

MCE treatment appears to work by suppressing the IL-4 cytokine and inhibiting the iNOS-mediated COX-2 induction pathway, as well as reducing inflammasome activation, suggesting a potential mechanism for its anti-inflammatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory effects of Capparis ecuadorica extract in phthalic-anhydride-induced atopic dermatitis of IL-4/Luc/CNS-1 transgenic mice. Song, BR., Lee, SJ., Kim, JE., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6126071/

Biological Activities, Health Benefits, and Therapeutic ... Considering the anti-inflammatory properties of Avns and their capacity to inhibit smooth muscle cell proliferation and increase NO production, these compounds ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772502225007371

Combined effects of genotype and harvest year on the ... Our study aimed at screening the variation of AVNs in an oat population consisting of eleven winter and eight spring oat accessions harvested in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8624809/

Avenanthramides: Unique Bioactive Substances of Oat Grain ... Moreover, AVNs modulate multiple biological events, resulting in anti-inflammatory anti-itching and immunomodulatory effects. These ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2018/6015351

Biological Activities, Health Benefits, and Therapeutic ... Among oat constituents, Avns are known to suppress histamine release at very low doses, helping to plump up the skin, reduce wrinkles, and ...

5. jn.nutrition.org jn.nutrition.org/article/S0022-3166(22)09241-0/fulltext

Avenanthramides Are Bioavailable and Have Antioxidant ... Avenanthramides (AV), alkaloids occurring only in oats, may have anti-atherosclerotic activity, but there is no information concerning their bioavailability ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10807472/

Phenolic amides (avenanthramides) in oats – an update review The amount of AVN-A, the major oat phytoalexin, reaches a maximum level of 350 µg/g at 48 h after elicitor treatment, approximately two times higher than that ...

7. researchgate.net researchgate.net/publication/325087879_Avenanthramides_of_oats_Medicinal_importance_and_future_perspectives

Avenanthramides of oats: Medicinal importance and future ... Avenanthramides (Avns) are polyphenols found exclusively in oats. Consumption of oats has been linked with a decreased risk of several ...