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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This will be a randomized clinical trial examining the efficacy and safety of ARAT (intervention group) in patients with chronic GERD symptoms (typical symptoms of GERD, i.e. heartburn or acid reflux/regurgitation at least twice a week) for the last 6 months. Patients must have a positive pH test and a negative manometry (no treatment) procedure.

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.

Is ARAT treatment generally safe for humans?

ARAT treatments like abiraterone, enzalutamide, apalutamide, and darolutamide have been used for prostate cancer and can cause side effects like changes in hormone levels, muscle loss, and effects on the brain. However, these treatments are generally considered safe for use in humans, with side effects being monitored and managed by healthcare providers. ^{1 2 3 4 5}

Research Team

Prateek Sharma, MD

Principal Investigator

Kansas City VA Hospital

Madhav Desai, MD

Principal Investigator

Kansas City VA Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. Canada 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

5. France 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. [2023]