The Effectiveness of High Resolution Microendoscopy for People Living With HIV

NCT ID: NCT04563754

Last Updated: 2025-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-30
• Study Completion Date: 2025-03-28

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

mHRME (Mobile High resolution microendoscope)

Intervention Type: DIAGNOSTIC_TEST

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.

Proflavine Hemisulfate

Intervention Type: DRUG

Contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)) to use with the mHRME

High resolution anoscopy

Intervention Type: DIAGNOSTIC_TEST

Standard of care (SOC) HRA with Lugol's iodine will be performed.

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Proflavine Hemisulfate

Contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)) to use with the mHRME

Intervention Type: DRUG

High resolution anoscopy

Standard of care (SOC) HRA with Lugol's iodine will be performed.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

William Marsh Rice University

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Sharmila Anandasabapathy

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sharmilla Anandasabapathy, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Elizabeth Y Chiao, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Baylor College of Medicine

Houston, Texas, United States

M.D. Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Brenes D, Kortum A, Carns J, Mutetwa T, Schwarz R, Liu Y, Sigel K, Richards-Kortum R, Anandasabapathy S, Gaisa M, Chiao E. Automated In Vivo High-Resolution Imaging to Detect Human Papillomavirus-Associated Anal Precancer in Persons Living With HIV. Clin Transl Gastroenterol. 2023 Feb 1;14(2):e00558. doi: 10.14309/ctg.0000000000000558.

Reference Type: DERIVED

PMID: 36729506 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

H-44616 Anal HRME

Identifier Type: -

Identifier Source: org_study_id