A Randomized Trial to Evaluated the Suppressive Effect of Acyclovir on Rapidly Cleared HSV-2 Reactivation

• ClinicalTrials.gov Identifier: NCT00723229
• Recruitment Status: Completed
• First Posted: July 28, 2008
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Sponsor: University of Washington
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Christine Johnston, University of Washington

Study Description

Brief Summary:

We propose to study the episode rate, duration, and quantity of HSV-2 genital shedding in patients taking standard, FDA approved, CDC recommended doses of acyclovir (400 mg PO BID) for HSV-2 suppression compared to taking no medication to better define the effect of acyclovir on short bursts of rapidly cleared HSV-2 shedding. This study will be a randomized, open label, cross-over trial. We hypothesize that short bursts of HSV-2 reactivation will not be suppressed by acyclovir.

Condition or disease	Intervention/treatment	Phase
Genital Herpes	Drug: acyclovir	Phase 4

Detailed Description:

We propose to study the episode rate, duration, and quantity of HSV-2 genital shedding in patients taking standard, FDA approved, CDC recommended doses of acyclovir (400 mg PO BID) for HSV-2 suppression compared to taking no medication to better define the effect of acyclovir on short bursts of rapidly cleared HSV-2 shedding. This study will be a randomized, open label, cross-over trial.

We propose to perform this study in two study populations. Cohort 1 will be comprised of 25 HSV-2 seropositive, HIV seronegative adults, and Cohort 2 will be comprised of 25 HSV-2 seropositive, HIV seropositive adults with a CD4 count>250 cells/mm3. As suppression of HSV-2 using acyclovir is currently being studied in large, multi-center, international clinical trials as an HIV prevention strategy, these results will have broad implications for public health around the world.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Cross-Over Study to Evaluate the Suppressive Effect of Acyclovir on Rapidly Cleared Herpes Simplex Virus Type 2 Genital Reactivation Episodes in Herpes Simplex Virus-2 Seropositive Adults
• Study Start Date: August 2008
• Actual Primary Completion Date: July 2010
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1	Drug: acyclovir; Acyclovir 400 mg PO BID for 28 days
No Intervention: 2

Outcome Measures

Primary Outcome Measures :

1. Frequency of HSV-2 Total Shedding From the Genital Tract as Measured by PCR, Calculated Using a Per-day Shedding Rate in Participants Treated With Suppressive Acyclovir as Compared to no Medication in HIV Seronegative and HIV Seropositive Individuals. [ Time Frame: 9 weeks ]

Secondary Outcome Measures :

1. Quantity of HSV Detected, Median [ Time Frame: 9 weeks ]
   Median quantity of HSV detected, among swabs with any HSV detected
2. Number of Genital HSV Shedding Episodes [ Time Frame: 9 weeks ]
   The number of HSV shedding episodes. A shedding episode is defined as any number of positive swabs preceded and followed by 2 negative swabs
3. Duration of Genital HSV Shedding Episodes [ Time Frame: 9 weeks ]
   Median duration of HSV shedding episodes, in hours

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

COHORT 1: HIV seronegative

1. Older than 18 years;
2. HSV-2 seropositive by Western Blot;
3. not receiving any drugs with known anti-HSV-2 activity for study duration;
4. women of child bearing potential who are sexually active with men must be using a medically accepted method of contraception as judged by the investigator;
5. women of child-bearing potential must have a negative pregnancy test (urine) at screening visit;
6. in general good health, without other serious medical conditions and specifically with normal renal and hepatic function, as determined by the patient's medical history;
7. planning to remain resident in the area of the study center for the duration of the study participation;
8. HIV seronegative

COHORT 2: HIV seropositive

1. Older than18 years;
2. HSV-2 seropositive by Western Blot;
3. not receiving any drugs with known anti-HSV-2 activity for study duration;
4. women of child bearing potential who are sexually active with men must be using a medically accepted method of contraception as judged by the investigator;
5. women of child-bearing potential must have a negative pregnancy test (urine) at screening visit;
6. in general good health, without other serious medical conditions and specifically with normal renal and hepatic function, as determined by the patient's medical history;
7. planning to remain resident in the area of the study center for the duration of the study participation;
8. HIV seropositive
9. CD4 count over 250 cell/mm3
10. Not taking antiretroviral therapy

Exclusion Criteria:

For both cohorts:

1. hypersensitivity to acyclovir or valacyclovir;
2. pregnant women;
3. Taking immunosuppressive therapies, such as chronic oral steroids or immune modulatory drugs.

For cohort 2:

1. CD4 count<250 cell/mm3
2. Taking antiretroviral therapy at the time of study entry

Contacts and Locations

Locations

United States, Washington

University of Washington Virology Research Clinic

Seattle, Washington, United States, 98122

Sponsors and Collaborators

University of Washington

National Institutes of Health (NIH)

Investigators

• Principal Investigator: Christine Johnston, MD, MPH; University of Washington

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Johnston C, Saracino M, Kuntz S, Magaret A, Selke S, Huang ML, Schiffer JT, Koelle DM, Corey L, Wald A. Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials. Lancet. 2012 Feb 18;379(9816):641-7. doi: 10.1016/S0140-6736(11)61750-9. Epub 2012 Jan 4. Erratum in: Lancet. 2012 Feb 18;379(9816):616.

• Responsible Party: Christine Johnston, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT00723229
• Other Study ID Numbers: 34187-B; U19AI031448 ( U.S. NIH Grant/Contract )
• First Posted: July 28, 2008
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Last Verified: March 2017

Additional relevant MeSH terms:

Herpes Genitalis; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; Herpes Simplex; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Acyclovir; Antiviral Agents; Anti-Infective Agents