Trial Outcomes & Findings for Enema Use and Acceptability in HIV Negative Men Who Have Sex With Men (NCT NCT00696618)

Results Overview

Endoscopy will be performed to obtain biopsy specimens at baseline and following each inpatient enema exposure. Samples will be obtained at each flexible sigmoidoscopy and set aside for batch sectioning and H\&E staining. Slides will be reviewed and scored by a qualified pathologist blinded to treatment assignment using a qualitative scoring system. This scoring system uses semi-quantitative scoring that focuses on acute toxicity to epithelial cell layer similar to that seen in animal studies. This is a categorical grading scale, where 0 = Epithelial surface intact;1 = \<1/3 of surface denuded; 2 = 1/3 - 2/3rds of surface denuded;3 = More than 2/3rds of surface denuded. Six separate biopsies for each subject and each treatment intervention were analyzed in a multi-level analysis. In comparison with the baseline condition (no intervention), the odds and 95% confidence interval (CI) of having a higher epithelial denudation score were calculated for each intervention.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

9 participants

Primary outcome timeframe

One hour following enema exposure

Results posted on

2017-04-28

Participant Flow

Study participants were recruited to the outpatient clinical unit via a volunteer screening database.Similarly, individuals may have responded to advertisements posted throughout the Johns Hopkins Medical Institutions or via word of mouth from other research participants. Individuals were recruited between 10/10/07 and 01/06/09.

Seventeen subjects were recruited. Eight individuals did not meet screening criteria and were not enrolled.

Participant milestones

Participant milestones
Measure	Tap Water/Normosol-R/Fleet Tap water enema (hypo-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 1), Followed by Normosol-R enema (iso-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home(Stage 2), Followed by Fleet enema (hyper-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 3) Fleet Enema: hyper-osmolar preparation tap water enema: hypo-osmolar preparation Normosol-R enema: iso-osmolar preparation	Normosol-R/Fleet/Tap Water Normosol-R enema (iso-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 1), Followed by Fleet enema (hyper-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 2), Followed by Tap water enema (hypo-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 3) Fleet Enema: hyper-osmolar preparation tap water enema: hypo-osmolar preparation Normosol-R enema: iso-osmolar preparation	Fleet/Tap Water/Normosol-R Fleet enema (hyper-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 1), Followed by Tap water enema (hypo-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 2), Followed by Normosol-R enema(iso-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 3) Fleet Enema: hyper-osmolar preparation tap water enema: hypo-osmolar preparation Normosol-R enema: iso-osmolar preparation
Overall Study STARTED	3	3	3
Overall Study COMPLETED	3	3	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Enema Use and Acceptability in HIV Negative Men Who Have Sex With Men

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tap Water/Normosol-R/Fleet n=3 Participants Tap water enema (hypo-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 1), Followed by Normosol-R enema (iso-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home(Stage 2), Followed by Fleet enema (hyper-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 3) Fleet Enema: hyper-osmolar preparation tap water enema: hypo-osmolar preparation Normosol-R enema: iso-osmolar preparation	Normosol-R/Fleet/Tap Water n=3 Participants Normosol-R enema (iso-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 1), Followed by Fleet enema (hyper-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 2), Followed by Tap water enema (hypo-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 3) Fleet Enema: hyper-osmolar preparation tap water enema: hypo-osmolar preparation Normosol-R enema: iso-osmolar preparation	Fleet/Tap Water/Normosol-R n=3 Participants Fleet enema (hyper-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 1), Followed by Tap water enema (hypo-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 2), Followed by Normosol-R enema(iso-osmolar) administered rectally 125 mL one time in the clinic, then self-administered on three separate occasions at home (Stage 3) Fleet Enema: hyper-osmolar preparation tap water enema: hypo-osmolar preparation Normosol-R enema: iso-osmolar preparation	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: One hour following enema exposure

Population: All participants who received one dose of each intervention and completed all study visits were included in the analysis.

Endoscopy will be performed to obtain biopsy specimens at baseline and following each inpatient enema exposure. Samples will be obtained at each flexible sigmoidoscopy and set aside for batch sectioning and H\&E staining. Slides will be reviewed and scored by a qualified pathologist blinded to treatment assignment using a qualitative scoring system. This scoring system uses semi-quantitative scoring that focuses on acute toxicity to epithelial cell layer similar to that seen in animal studies. This is a categorical grading scale, where 0 = Epithelial surface intact;1 = \<1/3 of surface denuded; 2 = 1/3 - 2/3rds of surface denuded;3 = More than 2/3rds of surface denuded. Six separate biopsies for each subject and each treatment intervention were analyzed in a multi-level analysis. In comparison with the baseline condition (no intervention), the odds and 95% confidence interval (CI) of having a higher epithelial denudation score were calculated for each intervention.

Outcome measures

Outcome measures
Measure	Hypo-osmolar Enema n=54 colon biopsies Hypo-osmolar Tap water enema	Iso-osmolar Enema n=54 colon biopsies Normosol-R Iso-osmolar enema	Hyper-osmolar Enema n=54 colon biopsies Fleet Hyper-osmolar enema
Mucosal Toxicity Using Histopathology	0.6 units on a scale Interval 0.2 to 1.7	0.5 units on a scale Interval 0.2 to 1.5	4.2 units on a scale Interval 1.7 to 10.1

SECONDARY outcome

Timeframe: 24 hours following each intervention

Population: All participants who received one dose of each intervention and completed all study visits were included in the analysis.

Percent of radiolabel dose administered was determined by plasma sampling at standardized intervals over 24 hours. AUC was then calculated using the trapezoidal rule and reported as x10 log 7 microcurie-hours/mL

Outcome measures

Outcome measures
Measure	Hypo-osmolar Enema n=9 Participants Hypo-osmolar Tap water enema	Iso-osmolar Enema n=9 Participants Normosol-R Iso-osmolar enema	Hyper-osmolar Enema n=9 Participants Fleet Hyper-osmolar enema
Radiolabel Area Under the Curve (AUC 0-24 hr)	21.4 10 log 7 microcurie-hours/mL Interval 17.4 to 44.9	19.7 10 log 7 microcurie-hours/mL Interval 8.4 to 27.4	9.4 10 log 7 microcurie-hours/mL Interval 8.7 to 13.0

SECONDARY outcome

Timeframe: two hours following dosing of intervention

Population: All participants who received one dose of each intervention and completed all study visits were included in the analysis.

Mean proximal residence distance of radio-signal from anus as measured on SPECT/CT

Outcome measures

Outcome measures
Measure	Hypo-osmolar Enema n=9 Participants Hypo-osmolar Tap water enema	Iso-osmolar Enema n=9 Participants Normosol-R Iso-osmolar enema	Hyper-osmolar Enema n=9 Participants Fleet Hyper-osmolar enema
D(Average) at Two Hours	8.6 centimeters Interval 6.8 to 11.8	20.6 centimeters Interval 17.4 to 25.6	7.7 centimeters Interval 0.0 to 14.4

Adverse Events

Hypo-osmolar Enema

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Iso-osmolar Enema

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Hyper-osmolar Enema

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Hypo-osmolar Enema n=9 participants at risk Hypo-osmolar Tap water enema	Iso-osmolar Enema n=9 participants at risk Normosol-R Iso-osmolar enema	Hyper-osmolar Enema n=9 participants at risk Fleet Hyper-osmolar enema
Investigations Procedure-related	44.4% 4/9 • Number of events 7	22.2% 2/9 • Number of events 3	33.3% 3/9 • Number of events 5
Product Issues GI complaints thought related to study product	0.00% 0/9	11.1% 1/9 • Number of events 1	11.1% 1/9 • Number of events 1
Gastrointestinal disorders GI complaints other	11.1% 1/9 • Number of events 1	11.1% 1/9 • Number of events 1	22.2% 2/9 • Number of events 2
Nervous system disorders Dizzyness	0.00% 0/9	0.00% 0/9	11.1% 1/9 • Number of events 1
Skin and subcutaneous tissue disorders Facial cut	11.1% 1/9 • Number of events 1	0.00% 0/9	0.00% 0/9

Additional Information

Associate Director, Drug Development Unit

Johns Hopkins School of Medicine

Phone: (410)641-8762

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place