Dataset Information

A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4⁺ cell distribution in the human rectal mucosa.

ABSTRACT: To reduce HIV transmission, locally applied pre-exposure prophylaxis (PrEP) products for anorectal use will be important complements to oral and injectable PrEP products already available. It is critical to preserve an intact rectal epithelium and avoid an influx of mucosal HIV target cells with such product use. In this phase 1 clinical trial, we evaluated application of a topical rectal douche product containing Q-Griffithsin (Q-GRFT). Colorectal tissue samples were obtained via sigmoidoscopy at baseline, 1 and 24 h after single-dose exposure in 15 healthy volunteers. In situ staining for epithelial junction markers and CD4⁺ cells were assessed as an exploratory endpoint. A high-throughput, digitalized in situ imaging analysis workflow was developed to visualize and quantify these HIV susceptibility markers. We observed no significant differences in epithelial distribution of E-cadherin, desmocollin-2, occludin, claudin-1, or zonula occludens-1 when comparing the three timepoints or Q-GRFT versus placebo. There were also no differences in %CD4⁺ cells within the epithelium or lamina propria in any of these comparisons. In conclusion, the rectal epithelium and CD4⁺ cell distribution remained unchanged following topical application of Q-GRFT. In situ visualization of HIV susceptibility markers at mucosal sites could be useful to complement standard product safety assessments.

SUBMITTER: Franzen Boger M

PROVIDER: S-EPMC10169179 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4<sup>+</sup> cell distribution in the human rectal mucosa.

Franzén Boger Mathias M Benhach Nora N Hasselrot Tyra T Brand Rhonda M RM Rohan Lisa C LC Wang Lin L McGowan Ian I Edick Stacey S Ho Ken K Meyn Leslie L Matoba Nobuyuki N Palmer Kenneth E KE Broliden Kristina K Tjernlund Annelie A

Scientific reports 20230509 1

To reduce HIV transmission, locally applied pre-exposure prophylaxis (PrEP) products for anorectal use will be important complements to oral and injectable PrEP products already available. It is critical to preserve an intact rectal epithelium and avoid an influx of mucosal HIV target cells with such product use. In this phase 1 clinical trial, we evaluated application of a topical rectal douche product containing Q-Griffithsin (Q-GRFT). Colorectal tissue samples were obtained via sigmoidoscopy ...[more]

PMID: 37161022

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Project description:An 87-year-old-man with prostate-cancer-stage-T1c-Gleason-6 treated with radiotherapy in 1996, recurrent prostate cancer treated with leuprolide hormonal therapy in 2009, and bladder-urothelial-carcinoma in situ treated with Bacillus-Calmette-Guerin and adriamycin in 2010, presented in 2015 with painless, bright red blood per rectum coating stools daily for 5 mo. Rectal examination revealed bright red blood per rectum; and a hard, fixed, 2.5 cm × 2.5 cm mass at the normal prostate location. The hemoglobin was 7.6 g/dL (iron saturation = 8.4%, indicating iron-deficiency-anemia). Abdominopelvic-CT-angiography revealed focal wall thickening at the bladder neck; a mass containing an air cavity replacing the normal prostate; and adjacent rectal invasion. Colonoscopy demonstrated an ulcerated, oozing, multinodular, friable, 2.5 cm × 2.5 cm mass in anterior rectal wall, at the usual prostate location. Histologic and immunohistochemical analysis of colonoscopic biopsies of the mass revealed poorly-differentiated-carcinoma of urothelial origin. At visceral angiography, the right-superior-rectal-artery was embolized to achieve hemostasis. The patient subsequently developed multiple new metastases and expired 13 mo post-embolization. Comprehensive literature review revealed 16 previously reported cases of rectal involvement from bladder urothelial carcinoma, including 11 cases from direct extension and 5 cases from metastases. Patient age averaged 63.7 ± 9.6 years (all patients male). Rectal involvement was diagnosed on average 13.5 ± 11.8 mo after initial diagnosis of bladder urothelial carcinoma. Symptoms included constipation/gastrointestinal obstruction-6, weight loss-5, diarrhea-3, anorexia-3, pencil thin stools-3, tenesmus-2, anorectal pain-2, and other-5. Rectal examination in 9 patients revealed annular rectal constriction-6, and rectal mass-3. The current patient had the novel presentation of daily bright red blood per rectum coating the stools simulating hemorrhoidal bleeding; the novel mechanism of direct bladder urothelial carcinoma extension into rectal mucosa via the prostate; and the novel aforementioned colonoscopic findings underlying the clinical presentation.

Project description:ObjectivesPatient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis.DesignSPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection.SettingThe phase 1 clinical trial took place at a University Outpatient Clinical Trials Unit from November 2021 to September 2023.ParticipantsThe initial SPRAY PAL questionnaire was piloted among healthy volunteers ages 25 to 55 in phase 1a of the clinical trial (N=18) and revised for administration in phase 1b for participants ages 24-59 (N=22).ResultsSpearman correlations tested convergent and discriminant validity. Internal consistency was assessed using Cronbach's alpha, and test-retest reliability was assessed using intraclass correlation coefficients of responses collected from three repeated questionnaire administrations. The initial version demonstrated excellent internal consistency. The revised version demonstrated very good internal consistency after removal of one item (alpha=0.739). Excellent test-retest reliability (intraclass coefficient=0.927) and adequate convergent (r's=0.208-0.774) and discriminant (r's=0.123-0.392) validity were achieved. Subscales adequately distinguished between the constructs of acceptability, feasibility and tolerability.ConclusionsThe SPRAY PAL product acceptability questionnaire is a valid and reliable patient-reported outcomes measure that can be considered a credible tool for assessing patient-reported information about product acceptability, feasibility of use, tolerability of product and side effects and cost of product for novel intranasal drug formulations. The SPRAY PAL is generalisable, and items may be readily adapted to assess other intranasal formulations.Trial registration numbersNCT05122260 and NCT05437029.

Dataset Information

A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4⁺ cell distribution in the human rectal mucosa.

Publications

A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4<sup>+</sup> cell distribution in the human rectal mucosa.

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Dataset Information

A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4+ cell distribution in the human rectal mucosa.

Publications

A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4&lt;sup&gt;+&lt;/sup&gt; cell distribution in the human rectal mucosa.

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OmicsDI is part of the ELIXIR infrastructure

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A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4⁺ cell distribution in the human rectal mucosa.

A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4<sup>+</sup> cell distribution in the human rectal mucosa.