Anal High Grade Squamous Intraepithelial LesionPhase 1/2NCT04563754

The Effectiveness of High Resolution Microendoscopy for People Living With HIV

A Phase 1/2 study testing mHRME (Mobile High resolution microendoscope), Proflavine Hemisulfate and High resolution anoscopy in people with Anal High Grade Squamous Intraepithelial Lesion, run by Baylor College of Medicine at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Anal High Grade Squamous Intraepithelial Lesion
What is being tested?: mHRME (Mobile High resolution microendoscope), Proflavine Hemisulfate and High resolution anoscopy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 163 participants
Where: 3 sitesUnited States
Study dates: 30 Jul 2019to 28 Mar 2025
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

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

Other trials in United States

About this study

Official title: 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.

Read the 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
Being tested: mHRME (Mobile High resolution microendoscope), Proflavine Hemisulfate, High resolution anoscopy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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:
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 HemisulfateDrug
Contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)) to use with the mHRME
High resolution anoscopyDiagnostic test
Standard of care (SOC) HRA with Lugol's iodine will be performed.

Study groups in NCT04563754
Study group	Role	What they receive
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. Receives: Diagnostic Test: mHRME (Mobile High resolution microendoscope); Drug: Proflavine Hemisulfate; Diagnostic Test: High resolution anoscopy

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1 day

Secondary outcomes (2)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jul 201928 Mar 2025

First posted24 Sep 2020
Study start30 Jul 2019
Primary completion28 Mar 2024
Study completion28 Mar 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Anal High Grade Squamous Intraepithelial LesionStudies of the same condition, open and under way.
More trials run by Baylor College of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Screening
Allocation: Not applicable
Intervention model: Single group
Model description: This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.
Masking: None (open label)
Enrolment: 163 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04563754
Sponsor's protocol ID: H-44616 Anal HRME
Status last verified: Apr 2025
First submitted: 10 Mar 2020
Last updated: 23 Apr 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 36729506

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
CASCADE 2002: PROTECT Study, "PRObiotics to TrEat Anal preCancer Trial
HSIL, High Grade Squamous Intraepithelial Lesion, HPV-Related Squamous Cell Carcinoma
Active, not recruiting
Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico
AIDS-Related Anal Carcinoma, AIDS-Related Cervical Carcinoma
Active, not recruitingObservational study
Anal High-risk HPV, HSIL, and Microbiome Among Hispanic Peoples Living With HIV (PLWH)
Human Immunodeficiency Virus, Human Papillomavirus-Related Anal Squamous Cell Carcinoma
RecruitingPhase 1
Safety of Anal Curcumin
Anal High Grade Squamous Intraepithelial Lesion
Not yet recruitingPhase 1
Use of ACU-D1 in HPV Associated Vulvar and Perianal Lesions in People With HIV
Human Papilloma Virus, Human Immunodeficiency Virus

All Anal High Grade Squamous Intraepithelial Lesion trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effectiveness of High Resolution Microendoscopy (HRME) in High Grade Intraepithelial Lesions (HSIL) Diagnosis for People Living With HIV
ClinicalTrials.gov ID: NCT04563754
Acronym / sponsor ID: H-44616 Anal HRME
Conditions: Anal High Grade Squamous Intraepithelial Lesion
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 163 participants (actual)
Lead sponsor: Baylor College of MedicineUniversity, hospital or other
Collaborators: Icahn School of Medicine at Mount Sinai, William Marsh Rice University, University of California, San Francisco, The University of Texas Health Science Center, Houston, M.D. Anderson Cancer Center, Medical University of South Carolina
Study start: 30 Jul 2019 (actual)
Primary completion: 28 Mar 2024 (actual)
Study completion: 28 Mar 2025 (actual)
First posted: 24 Sep 2020 (actual)
Results: Posted 23 Apr 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Screening
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.

Arm	Type	Receives
mHRME	Experimental	Diagnostic Test: mHRME (Mobile High resolution microendoscope), Drug: Proflavine Hemisulfate, Diagnostic Test: High resolution anoscopy5-10 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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	mHRME
Proflavine HemisulfateContrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)) to use with the mHRME	Drug	mHRME
High resolution anoscopyStandard of care (SOC) HRA with Lugol's iodine will be performed.	Diagnostic test	mHRME

Primary outcome

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.

2 secondary outcomes

Procedure Efficiency
Time frame: 1 day
Procedure Time
Time frame: 1 day

Results and safety

Results posted to the registry on 23 Apr 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tisch Cancer Institute Mount Sinai	79	68
Thomas Street Health Center	66	60
Training Set Cohort	18	0

Primary outcome: Performance Characteristics: Sensitivity (SN), Specificity (SP), Positive Predictive Value (PPV) and Negative Predictive Values (NPV)

Time frame: 1 day. Number (95% Confidence Interval). Unit: percentage of biopsies

Measure	Tisch Cancer Institute Mount Sinai n = 68	Thomas Street Health Center n = 60	Training Set Cohort n = 9
HRA - SN	90.0 (76.3 to 97.2)	76.9 (56.4 to 91.0)	100.0 (66.4 to 100.0)
HRA - SP	65.6 (52.3 to 77.3)	48.0 (37.9 to 58.2)	90.9 (58.7 to 99.8)
HRA - PPV	63.2 (49.3 to 75.6)	27.8 (17.9 to 39.6)	90.0 (55.5 to 99.7)
HRA - NPV	90.9 (78.3 to 97.5)	88.9 (77.4 to 95.8)	100.0 (69.2 to 100.0)
HRME - SN	90.0 (76.3 to 97.2)	92.3 (74.9 to 99.1)	100.0 (66.4 to 100.0)
HRME - SP	67.2 (54.0 to 78.7)	68.0 (57.9 to 77.0)	100.0 (71.5 to 100.0)
HRME - PPV	64.3 (50.4 to 76.6)	42.9 (29.7 to 56.8)	100.0 (66.4 to 100.0)
HRME - NPV	91.1 (78.8 to 97.5)	97.1 (90.1 to 99.7)	100.0 (71.5 to 100.0)

Population analysed: 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.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tisch Cancer Institute Mount Sinai	0 of 79 (0%)	0 of 79 (0%)	0 of 79
Thomas Street Health Center	0 of 66 (0%)	0 of 66 (0%)	0 of 66
Training Set Cohort	0 of 18 (0%)	0 of 18 (0%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36729506Brenes 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.

Related trials for Anal High Grade Squamous Intraepithelial Lesion

RecruitingPhase 2
CASCADE 2002: PROTECT Study, "PRObiotics to TrEat Anal preCancer Trial
HSIL, High Grade Squamous Intraepithelial Lesion, HPV-Related Squamous Cell Carcinoma
Active, not recruiting
Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico
AIDS-Related Anal Carcinoma, AIDS-Related Cervical Carcinoma
Active, not recruitingObservational study
Anal High-risk HPV, HSIL, and Microbiome Among Hispanic Peoples Living With HIV (PLWH)
Human Immunodeficiency Virus, Human Papillomavirus-Related Anal Squamous Cell Carcinoma
RecruitingPhase 1
Safety of Anal Curcumin
Anal High Grade Squamous Intraepithelial Lesion
Not yet recruitingPhase 1
Use of ACU-D1 in HPV Associated Vulvar and Perianal Lesions in People With HIV
Human Papilloma Virus, Human Immunodeficiency Virus

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sharmilla Anandasabapathy, MD principal investigator

Baylor College of Medicine

Elizabeth Y Chiao, MD principal investigator

M.D. Anderson Cancer Center

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Performance Characteristics: Sensitivity (SN), Specificity (SP), Positive Predictive Value (PPV) and Negative Predictive Values (NPV) (time frame: 1 day). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04563754, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025.