The Effectiveness of High Resolution Microendoscopy for People Living With HIV

Anal High Grade Squamous Intraepithelial Lesion Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04563754
• Other study ID #: H-44616
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 30, 2019
• Est. completion date: March 28, 2024

Study information

• Verified date: May 2024
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: March 28, 2024
• Est. primary completion date: March 28, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anal High Grade Squamous Intraepithelial Lesion
• Carcinoma in Situ
• Carcinoma, Squamous Cell
• Squamous Intraepithelial Lesions of the Cervix

Intervention

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: contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)), 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.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (7)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Performance characteristics: Sensitivity (SN), Specificity (SP), positive predictive value (PPV) and negative predictive values (NPV)	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 year
Secondary	Procedure efficiency	Diagnostic yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who received biopsies.	1 year
Secondary	Procedure time	Total procedure time (HRA+HRME+biopsies) vs HRME time alone	1 day