NCT04563754

The Effectiveness of High Resolution Microendoscopy for People Living With HIV

The Effectiveness of High Resolution Microendoscopy (HRME) in High Grade Intraepithelial Lesions (HSIL) Diagnosis for People Living With HIV

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 163 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The investigators have developed a portable, battery-operated, mobile high-resolution microendoscope (mHRME) that provides subcellular images of the anal epithelium, delineating the cellular and morphologic changes associated with neoplasia. The investigators' central hypothesis is that this 'optical' approach will increase the efficiency, clinical impact, and cost-effectiveness of the current standard of high-resolution anoscopy(HRA)-guided biopsy, thus facilitating usage by less-experienced clinicians in community-based or low-resource settings. To validate this, the investigators will conduct a study to determine the efficiency and diagnostic characteristics of the mHRME 'optical biopsy' approach versus the current standard of HRA-based tissue biopsy. Successful results will allow for improved efficacy and resource utilization for cancer screening in people living with HIV for anal cancer and other epithelial cancers including the cervix, oral cavity, bladder, and GI tract.

Detailed description

The investigators' central hypothesis is that using mHRME plus three-dimensional (3D) mapping as a diagnostic tool will improve the accuracy and efficiency of HSIL diagnoses. Additionally, the investigators hypothesize that the sensitivity (SN) specificity (SP), positive predictive value (PPV), and negative predictive value (NPV), as well as the receiver operating characteristic (ROC) curve for the identification of neoplasia on a per biopsy and per patient basis will be high. The investigators will first compare the HRA-directed biopsy (as the gold standard) to the results of the mHRME HSIL diagnosis. The SN of mHRME diagnosis in the detection of HSIL will be estimated with the binomial proportion of study participants who are positive for HSIL on HRA-guided biopsy at two thresholds of histology thresholds which are: 1) Anal intraepithelial neoplasia (AIN) 2+ threshold, and 2) AIN3+ threshold. SP will be estimated as the proportion of study participants who are negative for HSIL on HRA-guided biopsy at both thresholds. PPV and NPV will be estimated using the binomial proportion and 95% confidence interval (CI). In addition, Cohen's kappa statistic and ROC curves will be generated if patient characteristics such as low Clusters of differentiation 4 (CD4) count, combined antiretroviral treatment (cART) utilization, or high HIV viral load impact the determination of SN and SP. SN and SP of mHRME-based HSIL diagnosis will be estimated on a per lesion and per patient basis with 95% CI and compared by McNemar's test. A generalized linear model for logistic regression with multiple correlated outcomes will compare SN and SP of each method on a per biopsy and per patient basis. Primary Objective: To determine if the mHRME plus 3D mapping improves the accuracy of anal HSIL diagnosis compared to the gold standard of histologic diagnosis of HSIL by HRA-guided biopsy. Secondary Objectives: Determination whether HRME changes the decision to perform biopsy.

Conditions

• Anal High Grade Squamous Intraepithelial Lesion

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	mHRME (Mobile High resolution microendoscope)	Standard of care (SOC) high-resolution anoscopy (HRA) with Lugol's iodine will be performed. The unstained (abnormal) area will be evaluated with mHRME for optical biopsy diagnosis: 1. contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)), 2. the mHRME will then be inserted and imaging of abnormal tissues will be performed. This will add 2 to 6 minutes per procedure. This is a single-arm study where all subjects will receive both SOC HRA and experimental mHRME imaging.
DRUG	Proflavine Hemisulfate	Contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)) to use with the mHRME
DIAGNOSTIC_TEST	High resolution anoscopy	Standard of care (SOC) HRA with Lugol's iodine will be performed.

Timeline

• Start date: 2019-07-30
• Primary completion: 2024-03-28
• Completion: 2025-03-28
• First posted: 2020-09-24
• Last updated: 2025-04-23
• Results posted: 2025-04-23

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study