BK Virus in Salivary Gland Disease: Treating the Potential Etiologic Agent

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT02068846
• Collaborator: National Institute of Dental and Craniofacial Research (NIDCR) (NIH)
• Enrollment: 17
• Location: 1
• Arms: 2
• Actual Duration (Months): 21
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to analyze BK viral infection in salivary gland diseases; specifically, to determine a definitive relationship between BK Virus and HIV associated salivary gland disease (HIVSGD). Participants are adults HIV+SGD+ who will be randomized 1:1 to receive BK Virus antiviral (ciprofloxacin) or placebo for 28 days. Salivary function/protein secretion will be correlated with BK polyomavirus titers. It is expected that patients with HIV+SGD+ will have elevated oral BK polyomavirus viral loads and will benefit from Ciprofloxacin.

Condition or Disease	Intervention/Treatment	Phase
HIV; Salivary Gland Disease; Benign Lymphoepithelial Lesion	Drug: Ciprofloxacin; Drug: Placebo	Phase 3

Detailed Description

The study duration is 12 weeks with a baseline visit, a visit at 4 weeks and a visit at 12 weeks. At baseline participants are randomized to Ciprofloxacin or placebo and take the drug or placebo for 28 days. At subsequent visits BK polyomavirus presence and salivary gland function will be assessed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: BK Virus in Salivary Gland Disease
• Actual Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ciprofloxacin Active treatment twice daily for 28 days	Drug: Ciprofloxacin; Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.; Other Names: Cipro
Placebo Comparator: Placebo Placebo treatment twice daily for 28 days	Drug: Placebo; Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. BK Viral Status in Saliva at Week 4 [Week 4]

   Oral fluids will be assessed for evidence of BK Virus replication to determine whether Cipro administration inhibits BK Virus replication in participants with HIVSGD. Oral fluids will be assessed by real-time PCR to determine BK Virus status as positive or negative.

2. BK Viral Status in Saliva at Week 12 [Week 12]

   Oral fluids will be assessed for evidence of BK Virus replication to determine whether Cipro administration inhibits BK Virus replication in participants with HIVSGD. Oral fluids will be assessed by real-time PCR to determine BK Virus status as positive or negative.

Secondary Outcome Measures

1. Unstimulated Salivary Flow Rate at Week 4 [Week 4]

   To determine whether salivary gland function is improved or restored with the administration of Cipro in participants with HIVSGD. After sitting at rest for 1 minute, participants collect drool using 50-mL conical tubes. The 5-minute unstimulated whole saliva flow rate recorded and collected. Salivary hypofunction is defined as unstimulated whole saliva flow rate ≤ 0.1 mL/min. Normal salivary function is defined as > 0.1 mL/min.

2. Unstimulated Salivary Flow Rate at Week 12 [Week 12]

   To determine whether salivary gland function is improved or restored with the administration of Cipro in participants with HIVSGD. After sitting at rest for 1 minute, participants collect drool using 50-mL conical tubes. The 5-minute unstimulated whole saliva flow rate recorded and collected. Salivary hypofunction is defined as unstimulated whole saliva flow rate ≤0.1 mL/min. Normal salivary function is defined as >0.1 mL/min.

3. Number of Participants Reporting Dry Mouth "Yes/No" at Week 4 [Week 4]

   Participants were asked "Have you noticed any change in your salivary glands or in the dryness of your mouth"

4. Number of Participants Reporting Dry Mouth "Yes/No" at Week 12 [Week 12]

   Participants were asked "Have you noticed any change in your salivary glands or in the dryness of your mouth"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV positive with Salivary Gland Disease

• Ability to read and understand English

Exclusion Criteria:

• Allergy to the family of fluoroquinolones (including ciprofloxacin)

• Currently taking tizanidine

• Concurrently taking antiacids containing magnesium hydroxide or aluminum hydroxide

• Current use of Theophylline

• Previous tendon disorder such as Rheumatoid arthritis

• History of seizures

• Current use of phenytoin

• Current use of glyburide

• Current use of methotrexate

• Severe renal impairment (known creatinine clearance < 30 or on dialysis)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of North Carolina School of Dentistry	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• National Institute of Dental and Craniofacial Research (NIDCR)

Investigators

• Principal Investigator: Jennifer Webster-Cyriaque, DDS, PhD, The University of North Carolina School of Dentistry

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02068846
• Other Study ID Numbers: 12-0036; 1R21DE023046-01A1
• First Posted: Feb 21, 2014
• Last Update Posted: Jul 11, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by University of North Carolina, Chapel Hill: HIV; Salivary Gland Disease; Benign Lymphoepithelial Lesion; BK Polyomavirus
• Additional relevant MeSH terms: Salivary Gland Diseases; Ciprofloxacin

Study Results

Participant Flow

Arm/Group Title	Ciprofloxacin	Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
Period Title: Overall Study
STARTED	9	8
COMPLETED	8	7
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Ciprofloxacin	Placebo	Total
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.	Total of all reporting groups
Overall Participants	9	8	17
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	52.6	52.3	52.5
Sex: Female, Male (Count of Participants)
Female	2 22.2%	1 12.5%	3 17.6%
Male	7 77.8%	7 87.5%	14 82.4%
Race/Ethnicity, Customized (Count of Participants)
White non-Hispanic	3 33.3%	1 12.5%	4 23.5%
Black or African American	5 55.6%	4 50%	9 52.9%
Asian	0 0%	1 12.5%	1 5.9%
Hispanic or Latino	0 0%	2 25%	2 11.8%
Other	1 11.1%	0 0%	1 5.9%
Region of Enrollment (Count of Participants)
United States	9 100%	8 100%	17 100%
BK Virus Status in Saliva (Count of Participants)
BK Virus positive	8 88.9%	2 25%	10 58.8%
BK Virus negative	1 11.1%	5 62.5%	6 35.3%
Unstimulated Salivary Flow Rate (Count of Participants)
Normal salivary function	4 44.4%	1 12.5%	5 29.4%
Salivary Hypofunction	5 55.6%	6 75%	11 64.7%

Outcome Measures

1. Primary Outcome

Title	BK Viral Status in Saliva at Week 4
Description	Oral fluids will be assessed for evidence of BK Virus replication to determine whether Cipro administration inhibits BK Virus replication in participants with HIVSGD. Oral fluids will be assessed by real-time PCR to determine BK Virus status as positive or negative.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Two participants withdrew prior to Week 4

Arm/Group Title	Ciprofloxacin	Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
Measure Participants	8	7
BK Virus positive	3 33.3%	6 75%
BK Virus negative	5 55.6%	1 12.5%

2. Primary Outcome

Title	BK Viral Status in Saliva at Week 12
Description	Oral fluids will be assessed for evidence of BK Virus replication to determine whether Cipro administration inhibits BK Virus replication in participants with HIVSGD. Oral fluids will be assessed by real-time PCR to determine BK Virus status as positive or negative.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Two participants withdrew prior to Week 4

Arm/Group Title	Ciprofloxacin	Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
Measure Participants	8	7
BK Virus positive	3 33.3%	4 50%
BK Virus negative	5 55.6%	3 37.5%

3. Secondary Outcome

Title	Unstimulated Salivary Flow Rate at Week 4
Description	To determine whether salivary gland function is improved or restored with the administration of Cipro in participants with HIVSGD. After sitting at rest for 1 minute, participants collect drool using 50-mL conical tubes. The 5-minute unstimulated whole saliva flow rate recorded and collected. Salivary hypofunction is defined as unstimulated whole saliva flow rate ≤ 0.1 mL/min. Normal salivary function is defined as > 0.1 mL/min.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Two participants withdrew prior to Week 4 and one participant did not perform salivary flow collection.

Arm/Group Title	Ciprofloxacin	Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
Measure Participants	8	6
Normal salivary function	3 33.3%	1 12.5%
Salivary hypofunction	5 55.6%	5 62.5%

4. Secondary Outcome

Title	Unstimulated Salivary Flow Rate at Week 12
Description	To determine whether salivary gland function is improved or restored with the administration of Cipro in participants with HIVSGD. After sitting at rest for 1 minute, participants collect drool using 50-mL conical tubes. The 5-minute unstimulated whole saliva flow rate recorded and collected. Salivary hypofunction is defined as unstimulated whole saliva flow rate ≤0.1 mL/min. Normal salivary function is defined as >0.1 mL/min.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Two participants withdrew prior to Week 4 and two participants did not perform salivary flow collection.

Arm/Group Title	Ciprofloxacin	Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
Measure Participants	7	6
Normal salivary function	3 33.3%	1 12.5%
Salivary hypofunction	4 44.4%	5 62.5%

5. Secondary Outcome

Title	Number of Participants Reporting Dry Mouth "Yes/No" at Week 4
Description	Participants were asked "Have you noticed any change in your salivary glands or in the dryness of your mouth"
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ciprofloxacin	Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
Measure Participants	8	7
Change = Yes	2 22.2%	1 12.5%
Change = No	6 66.7%	6 75%

6. Secondary Outcome

Title	Number of Participants Reporting Dry Mouth "Yes/No" at Week 12
Description	Participants were asked "Have you noticed any change in your salivary glands or in the dryness of your mouth"
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ciprofloxacin	Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.	Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
Measure Participants	8	7
Change = Yes	2 22.2%	1 12.5%
Change = No	6 66.7%	6 75%

Adverse Events

Arm/Group Title	Ciprofloxacin		Placebo
Arm/Group Description	Active treatment twice daily for 28 days Ciprofloxacin: Over encapsulated Ciprofloxacin 500 mg will be taken twice daily for 28 days.		Placebo treatment twice daily for 28 days Placebo: Placebo will over encapsulated to match active treatment, taken twice daily for 28 days.
All Cause Mortality
	Ciprofloxacin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/8 (0%)
Serious Adverse Events
	Ciprofloxacin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Ciprofloxacin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		0/8 (0%)
Skin and subcutaneous tissue disorders
Rash	1/9 (11.1%)	1	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.