The Effectiveness of High Resolution Microendoscopy for People Living With HIV

April 8, 2025 updated by: Sharmila Anandasabapathy, Baylor College of Medicine

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

163

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Consentable patients with documented HIV disease
  • Either: 1) previously documented HSIL or 2) abnormal anal cytology within the past 2 years
  • Ages 18 years and older
  • Seen at the Baylor-affiliated Thomas Street Clinic (TSC), Mount Sinai Hospital and affiliated clinics

Exclusion Criteria:

  • Unable to undergo routine anoscopy
  • Allergy or prior reaction to the fluorescent contrast agent Proflavine or Iodine
  • Unable to give informed consent
  • Current or prior history of Invasive Anal Cancer
  • Known permanent or irreversible bleeding disorder, or other hematologic disorder that in the opinion of the investigator would place the patient at increased risk for adverse outcome from the procedure
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: mHRME

5-10 ml of proflavine hemisulfate (0.01%) will be applied on the anal epithelium. The mHRME will then be inserted and imaging of abnormal tissues will be performed.

This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) 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: 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.

Diagnostic test: High resolution anoscopy
Standard of care (SOC) HRA with Lugol's iodine will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Performance Characteristics: Sensitivity (SN), Specificity (SP), Positive Predictive Value (PPV) and Negative Predictive Values (NPV)
Time Frame: 1 day
The primary outcome of this study is to measure the operating characteristics including SN, SP, PPV and NPV comparing the physician- and algorithm- guided HRME-based image compared to the Lugol's- guided physician diagnosis of HSIL during HRA. Gold standard consensus pathology was used and pathology data needs to be obtained, verified, and entered.
1 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Procedure Efficiency
Time Frame: 1 day
Diagnostic yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who received biopsies.
1 day
Procedure Time
Time Frame: 1 day
Total procedure time (HRA+HRME+biopsies) vs HRME time alone
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Collaborators

Medical University of South Carolina
M.D. Anderson Cancer Center
The University of Texas Health Science Center, Houston
Icahn School of Medicine at Mount Sinai
University of California, San Francisco
William Marsh Rice University

Investigators

  • Principal Investigator: Sharmilla Anandasabapathy, MD, Baylor College of Medicine
  • Principal Investigator: Elizabeth Y Chiao, MD, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2019

Primary Completion (Actual)

March 28, 2024

Study Completion (Actual)

March 28, 2025

Study Registration Dates

First Submitted

March 10, 2020

First Submitted That Met QC Criteria

September 22, 2020

First Posted (Actual)

September 24, 2020

Study Record Updates

Last Update Posted (Actual)

April 23, 2025

Last Update Submitted That Met QC Criteria

April 8, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-44616 Anal HRME

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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