Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Icahn School of Medicine at Mount Sinai | OTHER |
| William Marsh Rice University | OTHER |
| University of California, San Francisco | OTHER |
| The University of Texas Health Science Center, Houston |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mHRME | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mHRME (Mobile High resolution microendoscope) | 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:
This is a single-arm study where all subjects will receive both SOC HRA and experimental mHRME imaging. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 day |
| Measure | Description | Time Frame |
|---|---|---|
| Procedure Efficiency | Diagnostic yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who received biopsies. | 1 day |
| Procedure Time | Total procedure time (HRA+HRME+biopsies) vs HRME time alone |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Sharmilla Anandasabapathy, MD | Baylor College of Medicine | Principal Investigator |
| Elizabeth Y Chiao, MD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States | ||
| Baylor College of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36729506 | Derived | 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. |
Not provided
Not provided
Not provided
Participants were recruited at two anal dysplasia clinics: Tisch Cancer Institute Mount Sinai in New York, NY, and Thomas Street Health Center in Houston, TX. At Tisch Cancer Institute Mount Sinai, participants were recruited between July 30, 2019, and September 28, 2021. At Thomas Street Health Center, participants were recruited between December 8, 2021, and March 28, 2023. Participants were consented and screened for eligibility at time of presentation to the two recruitment sites.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Tisch Cancer Institute Mount Sinai | Participants enrolled in the Tisch Cancer Institute Mount Sinai. |
| FG001 | Thomas Street Health Center | Participants enrolled in the Thomas Street Health Center, excluding the first 18 participants used as test subjects. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| HRME Procedure |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 24, 2023 |
Not provided
Not provided
| OTHER |
| M.D. Anderson Cancer Center | OTHER |
| Medical University of South Carolina | OTHER |
This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.
Not provided
Not provided
No masking will be used in this study.
Not provided
|
| Proflavine Hemisulfate | 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 | Diagnostic Test | Standard of care (SOC) HRA with Lugol's iodine will be performed. |
|
| 1 day |
| Houston |
| Texas |
| 77030 |
| United States |
| M.D. Anderson Cancer Center | Houston | Texas | 77030 | United States |
| FG002 | Training Set Cohort | The first 18 participants enrolled in the Thomas Street Health Center as test subjects. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Follow up |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tisch Cancer Institute Mount Sinai | Participants enrolled in the Tisch Cancer Institute Mount Sinai. |
| BG001 | Thomas Street Health Center | Participants enrolled in the Thomas Street Health Center, excluding the first 18 participants used as test subjects. |
| BG002 | Training Set Cohort | The first 18 participants enrolled in the Thomas Street Health Center as test subjects. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The training set cohort (n=18) was used to optimize and develop the automated algorithms assessed for primary and secondary outcomes in the actual clinical study. In both the training set cohort and the clinical study, subjects unable to complete the HRME examination or undergo evaluation with the automated algorithm (n=26) were excluded. The remaining 137 evaluable subjects had images assessed by the algorithm and were analyzed separately by study site and the training set cohort. | Posted | Number | 95% Confidence Interval | percentage of biopsies | 1 day | Biopsies | Biopsies |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Procedure Efficiency | Diagnostic yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who received biopsies. | The training set cohort (n=18) was used to optimize and develop the automated algorithms assessed for primary and secondary outcomes in the actual clinical study. In both the training set cohort and the clinical study, subjects unable to complete the HRME examination or undergo evaluation with the automated algorithm (n=26) were excluded. The remaining 137 evaluable subjects had images assessed by the algorithm and were analyzed separately by study site and the training set cohort. | Posted | Number | 95% Confidence Interval | percentage of biopsies | 1 day | Biopsies | Biopsies |
| ||||||||||||||||||||||||||||||||||
| Secondary | Procedure Time | Total procedure time (HRA+HRME+biopsies) vs HRME time alone | The training set cohort (n=18) was used to optimize and develop the automated algorithms assessed for primary and secondary outcomes in the actual clinical study. In both the training set cohort and the clinical study, subjects who did not have both the procedure start and end times recorded were excluded (n=10). The remaining 153 subjects were analyzed separately by study site and the training set cohort. | Posted | Median | Inter-Quartile Range | minutes | 1 day |
|
|
Subjects will be contacted for adverse events 2 and 30 days from procedure. Patients with abnormal clinical findings will be followed until the condition resolves or stabilizes. Adverse events or serious adverse events that occur during the follow-up period will be recorded regardless of relatedness to the study procedure.
We will use Common Terminology Criteria for AE v5.0. Serious adverse events will count as Grade 3 (Severe or Medically Significant, but not Immediately Life Threatening: Hospitalization or Prolongation of Hospitalization Indicated; Disabling; Limiting Self Care ADL), Grade 4 (Life-threatening consequences; urgent intervention indicated) or Grade 5 (Death related to AE).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tisch Cancer Institute Mount Sinai | Participants enrolled in the Tisch Cancer Institute Mount Sinai. | 0 | 79 | 0 | 79 | 0 | 79 |
| EG001 | Thomas Street Health Center | Participants enrolled in the Thomas Street Health Center, excluding the first 18 participants used as test subjects. | 0 | 66 | 0 | 66 | 0 | 66 |
| EG002 | Training Set Cohort | The first 18 participants enrolled in the Thomas Street Health Center as test subjects. | 0 | 18 | 0 | 18 | 0 | 18 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Sharmila Anandasabapathy | Baylor College of Medicine | 713-798-8105 | Sharmila.Anandasabapathy@bcm.edu |
| Dec 13, 2024 |
| Prot_SAP_004.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 4, 2023 | Feb 15, 2023 | ICF_003.pdf |
Not provided
| ID | Term |
|---|---|
| D011370 | Proflavine |
| ID | Term |
|---|---|
| D000609 | Aminoacridines |
| D000166 | Acridines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Ongoing |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| HRA - PPV |
|
| HRA - NPV |
|
| HRME - SN |
|
| HRME - SP |
|
| HRME - PPV |
|
| HRME - NPV |
|
| Units | Counts |
|---|---|
| Participants |
|
| Biopsies |
|
|
| Counts |
|---|
| Participants |
|
|