ARAT for Acid Reflux

(AREA21 Trial)

Overseen By April Higbee, BSN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Midwest Veterans' Biomedical Research Foundation

Must not be taking: PPI medications

Disqualifiers: Hiatal hernia, Barrett's esophagus, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ARAT (Androgen Receptor Axis-Targeted therapies) to determine its effectiveness for people with chronic GERD (Gastroesophageal Reflux Disease), which causes symptoms like heartburn or acid reflux at least twice a week. Researchers aim to assess whether ARAT, involving a procedure in the stomach, is safe and effective compared to no treatment. Individuals who have experienced these symptoms for the past 6 months and have a positive pH test might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for GERD.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this ablation technique is safe for treating GERD?

Research has shown that ARAT, or anti-reflux mucosal ablation, is being explored as a treatment for acid reflux, particularly in individuals with chronic GERD (gastroesophageal reflux disease). This treatment uses hybrid argon plasma coagulation to target the gastric cardia, a part of the stomach.

The safety of ARAT in humans remains under investigation. The trial's "Not Applicable" phase designation suggests limited safety information may be available. In these early testing stages, researchers are gathering data on patient tolerance and potential side effects.

Without detailed safety information, staying informed and consulting healthcare professionals is crucial. They can help explain the risks and benefits based on current knowledge. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for acid reflux, which typically involve medications like antacids or proton pump inhibitors to reduce stomach acid, ARAT offers a new approach by using hybrid argon plasma coagulation. This technique targets the gastric cardia, aiming to ablate tissue in a way that can potentially reduce reflux without relying on daily medication. Researchers are excited about ARAT because it could provide a longer-lasting solution to acid reflux, reduce the need for constant medication, and offer relief to patients who don't respond well to current options.

What evidence suggests that ARAT might be an effective treatment for GERD?

Research has shown that ARAT, a procedure that removes tissue in the stomach using hybrid argon plasma coagulation, may help reduce acid reflux symptoms. In this trial, some participants will receive the ARAT treatment. Early findings suggest this treatment can lower the frequency and intensity of heartburn and acid regurgitation. Studies indicate that patients experience fewer symptoms and improved quality of life after ARAT. While more data is needed, these early results are promising for people with chronic GERD (gastroesophageal reflux disease). ^{1 2 3 6 7}

Who Is on the Research Team?

Prateek Sharma, MD

Principal Investigator

Kansas City VA Hospital

Madhav Desai, MD

Principal Investigator

Kansas City VA Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with chronic GERD, experiencing heartburn or acid reflux at least twice a week for the past 6 months. They must have confirmed acid reflux via a pH test but no major esophagus movement issues. Excluded are those with certain esophageal conditions, previous surgeries, severe liver disease, allergies to PPIs, and very large hiatal hernias.

Inclusion Criteria

Objective evidence of reflux disease (positive ambulatory pH study)

I have had heartburn or acid reflux at least twice a week for the last 6 months.

Exclusion Criteria

Allergic or intolerant to PPI medications

I have a large hiatal hernia over 3 cm and it's very severe.

Gastroparesis documented by abnormal gastric emptying time

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive anti-reflux mucosal ablation using hybrid argon plasma coagulation

12 months

Multiple visits (in-person) at 3, 6, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up assessments at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• ARAT
• Sham intervention (control)

Trial Overview The AREA Study is testing ARAT's effectiveness in treating chronic GERD symptoms against a sham (fake) procedure as control. Participants will be randomly assigned to either receive ARAT or the sham intervention to compare outcomes.

How Is the Trial Designed?

Group I: Anti-reflux mucosal ablation (ARAT) Active Control 1 Intervention

ablation in the gastric cardia using hybrid argon plasma coagulation

Group II: No treatment Placebo Group 1 Intervention

no ablation

ARAT is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Abiraterone for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in European Union as Enzalutamide for:

• Metastatic castration-resistant prostate cancer
• Non-metastatic castration-resistant prostate cancer

Approved in Japan as Apalutamide for:

• Metastatic castration-sensitive prostate cancer
• Non-metastatic castration-resistant prostate cancer

Approved in Canada as Darolutamide for:

• Non-metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Midwest Veterans' Biomedical Research Foundation

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

Darolutamide, an androgen receptor inhibitor, showed minimal impact on cerebral blood flow (CBF) in cognition-related brain regions, indicating a low risk of central nervous system side effects, which is beneficial for patients.

In contrast, enzalutamide significantly reduced CBF in multiple brain areas, suggesting potential cognitive risks associated with its use, highlighting the importance of considering CNS effects when choosing prostate cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. Williams, SCR., Mazibuko, N., O'Daly, O., et al.[2023]

ARAT agents like abiraterone acetate and enzalutamide improve survival rates in advanced prostate cancer but are associated with significant endocrine and metabolic side effects, such as hypertension and insulin resistance.

Darolutamide appears to have a safer side effect profile compared to other ARAT agents, suggesting that treatment for advanced prostate cancer should be personalized based on individual patient safety and risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer. Pyrgidis, N., Vakalopoulos, I., Sountoulides, P.[2021]

In a study of 55 patients with metastatic hormone-naive prostate cancer, no significant differences in muscle loss were observed between those receiving androgen deprivation therapy (ADT) alone or in combination with either abiraterone or enzalutamide.

Despite the lack of difference between treatment groups, all patients experienced decreases in skeletal muscle mass, emphasizing the need for strategies to preserve muscle during ADT for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the sarcopenic effect of androgen receptor-axis-targeted agents vs. androgen deprivation alone in patients with metastatic prostate cancer. Lawen, T., Masoumi-Ravandi, K., Rendon, RA., et al.[2023]

In a comparison of darolutamide with apalutamide and enzalutamide for treating nonmetastatic castration-resistant prostate cancer, no differences in metastasis-free survival were found, indicating similar efficacy among the treatments.

Darolutamide demonstrated a better safety profile, with significantly lower rates of falls, fractures, and rashes compared to apalutamide, and lower rates of dizziness and fatigue compared to enzalutamide, suggesting it may be a preferable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer. Halabi, S., Jiang, S., Terasawa, E., et al.[2021]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-gastroesophageal-reflux-1-2022-eac9e

ARAT for Acid Reflux (AREA21 Trial) This will be a randomized clinical trial examining the efficacy and safety of ARAT (intervention group) in patients with chronic GERD symptoms (typical ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40327314/

Real-world clinical outcomes of apalutamide versus ... Both treatments were generally well tolerated, though adverse events were more prevalent with apalutamide.

3. researchgate.net researchgate.net/publication/396871208_Adverse_events_of_androgen_receptor_pathway_inhibitors_in_prostate_cancer_from_real_world_data

(PDF) Adverse events of androgen receptor pathway ... Conclusion. Patients with mHSPC benefit from the combination of NAT with ADT, regardless of the presence or absence of VM (HR 0.67; 95 % CI 0.60 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5120984/

Androgen receptor axis-targeted agents - PubMed Central - NIH The advent of the new hormonal agents abiraterone acetate and enzalutamide have improved the prognosis of men with mCRPC.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2352396423000658

Targeting androgen receptor and the variants by an orally ... Although androgen deprivation therapy (ADT) is effective in alleviating tumor burden during early stages, virtually all disease presentations rapidly develop to ...

6. tandfonline.com tandfonline.com/doi/full/10.1080/17425255.2022.2122812

Treatment of non-metastatic castration-resistant prostate ... After some years, ADT may not be enough to control the prostate cancer. A type of medication called 'androgen receptor inhibitors' (ARIs), which prevent the ...

7. mdpi.com mdpi.com/1420-3049/25/10/2448

Second-Generation Androgen Receptor Antagonists as ... The combination therapy of bicalutamide with ADT is widely used by CSPC patients owing to the greater safety profile than ADT alone, even though it does not ...