HIVPhase 1NCT02569697
Development of Adherence Biomarkers for Multiple Microbicide and Multipurpose Prevention Technology (MPT) Dosage Forms
A Phase 1 study of HIV, run by CONRAD at 1 site in United States.
Trial summary
The purpose of this study is to develop markers for use of placebo vaginal products and measure markers of mucosal semen exposure among healthy women. The study will also monitor safety of placebo product use. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Volunteers must meet all of the following criteria prior to genital sampling at Visit 2:
- Age 18 to 50 years, inclusive
- General good health (by volunteer history and per investigator judgment) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease, and diabetes)
- History of Pap smears and follow-up consistent with standard medical practice as outlined in the Study Manual or willing to undergo a Pap smear at V1
- Willing to give voluntary consent and sign an informed consent form
- Willing and able to comply with protocol requirements
- Protected from pregnancy by:
- hysterectomy
- reliable methods of contraception other than male or female condoms, contraceptive IVR or male partner's vasectomy
- abstinence (IVR group only)
- or in a same sex relationship (IVR group only)
- For gel, insert or film assigned participants: Willing to engage in intercourse with a male sexual partner without the use of male or female condoms as required in the protocol
- For gel, insert or film assigned participants: In a mutually monogamous relationship with a male partner who:
- Is at least 18 years old
- Is not known to be HIV positive
- Has no known risk for STIs
- Has not undergone a vasectomy
- Is not known to have azoospermia
- Is willing and able to comply with protocol requirements regarding sexual activity/ abstinence
- Can engage with the participant in vaginal intercourse without condoms, as specified in the protocol 8.2. Exclusion Criteria
Volunteers must not meet any of the following criteria prior to genital sampling at Visit 2:
- Currently pregnant
- Currently breastfeeding or planning to breastfeed during the course of the study
- History of sensitivity/allergy to any component of the vaginal products for either the volunteer or her sexual partner, as applicable
- Use of vaginal douches, creams or gels, other than the study product, at any time during the study, beginning 7 days prior to V2
- In the last six months, either the volunteer or her sexual partner (as applicable) diagnosed with or treated for any STI. Note: Women with a history of genital herpes who have been asymptomatic for at least six months may be considered for eligibility
- Positive test for Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis or HIV
- Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.)
- Known current drug or alcohol abuse which could impact study compliance
- Participation in any other investigational trial within the last 30 days or planned participation in any other investigational trial during the study
- Abnormal finding on laboratory or physical examination or a social or medical condition in either the volunteer or her sexual partner (as applicable) which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
Trial locations and contacts
1 site in 1 country.
United States1 site
Eastern Virginia Medical School
Norfolk, Virginia, 23507
About this study
The purpose of this study is to develop markers for use of placebo vaginal products and measure markers of mucosal semen exposure among healthy women. The study will also monitor safety of placebo product use.
Read the detailed description
This is a Phase I, non-randomized, open label study in healthy, non-pregnant, HIV negative women, who are not at risk of pregnancy, and are at low risk for STIs (sexually transmitted infections). Participants will be assigned to use one of four placebo products: IVR (intravaginal ring) (approximately 20 participants), and vaginal insert, film or HEC universal placebo gel (approximately 10 participants each). Each woman will provide pre-product use vaginal swabs. Participants assigned to vaginal insert, film or gel will use products with and without timed intercourse with their male partner for a total of two doses of the product, will provide vaginal swabs post product use, and will be seen over 4 visits.
Participants assigned to IVR do not have to be sexually active with a male partner. IVR assigned participants will use a total of 3 IVRs, one at a time. IVR assigned participants will use the first IVR (IVR1) for approximately 24 - 36 hours (no exposure to semen during IVR1 use). IVR assigned participants will use a second IVR (IVR2) for approximately 7 - 10 days and a third IVR (IVR3) for approximately 28 - 32 days. During the use of IVR2 and IVR3, participants may engage in sexual intercourse, but it is not required. Women assigned to IVR use will be seen over 5 visits.
Once a woman completes the study cycle with one study product, she may elect to do another cycle using a different product after a wash-out period of at least 7 days, if she can comply with study product specific protocol requirements. She may elect to do up to four cycles, each with a different study product. For each cycle, V1 screening procedures will be repeated as indicated by symptoms and or participant history, as assessed by the investigator and as outlined in the study manual. If re-screening procedures are not indicated, the new cycle may start with Visit 2 (V2).
At Visit 1 (V1), volunteers will be consented and undergo procedures to confirm they are eligible to continue in the study. Participants will be counseled to refrain from vaginal activity, as applicable, for 48 hours prior to V2.
V2 should occur on days 3 - 10 of the menstrual cycle, or for participants who do not have regular menstrual cycles, when the participant is not having heavy menstrual bleeding. Once it has been confirmed that the participant meets all of the inclusion criteria and none of the exclusion criteria, baseline pre-product use vaginal swabs will be taken. Participants will be required to refrain from any vaginal activity until after Visit 3 (V3).
- Participants assigned to gel, film or insert, will insert one dose (Dose 1) vaginally in the clinic. Vaginal swabs will be obtained in the clinic approximately 15 minutes after product use. Participants will be given vaginal swabs for home use. Participants will be instructed to obtain vaginal swabs, at bedtime daily, for 7 days, starting at the first bedtime after V2. Vaginal swabs will be stored in the participant's refrigerator and returned to the clinic at V3. V3 will occur 7 - 10 days after V2.
- For participants assigned to the IVR, the IVR1 will be inserted by the participant in the clinic. The participant will leave IVR1 in place until V3, which will occur 24 - 36 hours after V2.
At V3:
- Participants assigned to gel, film or insert will return used vaginal swabs to the clinic. Additional vaginal swabs will be obtained in the clinic. Participants will vaginally insert one dose of their assigned product (Dose 2) in the clinic. Vaginal swabs will be obtained in the clinic approximately 15 minutes after product use. The participants will be instructed to have vaginal intercourse with her male sexual partner within approximately 12 hours (± 4 hours) after insertion of the product. They will obtain vaginal swabs, at bedtime daily, for 7 days, starting at the first bedtime after V3 and after timed intercourse, as above. Participants will be instructed to refrain from additional acts of vaginal intercourse or other vaginal activity until Visit 4 (V4). Vaginal swabs will be stored in the participant's refrigerator and returned to the clinic at V4. V4 will occur 7 - 10 days after V3.
- For participants assigned to the IVR, IVR1 will be removed at this visit. Post IVR1 use vaginal swabs will be obtained in the clinic. The second IVR (IVR2) will be inserted by the participant in the clinic. The participant will be instructed to leave the IVR2 in place until V4, which will occur 7 - 10 days after V3. IVR Participants may have vaginal intercourse (not required) during the use of IVR2 but should not have any other vaginal activity during the use of IVR2.
At V4:
- Participants assigned to gel, film or insert will return used vaginal swabs to the clinic. Additional vaginal swabs will be obtained in the clinic. Participants will be exited from the study at this visit or they may elect to use a different study product.
- For participants assigned to the IVR, IVR2 will be removed at this visit. Post IVR2 use vaginal swabs will be obtained in the clinic. The third IVR (IVR3) will be inserted by the participant in the clinic. The participant will leave IVR3 in place until Visit 5 (V5), which will occur 28 - 32 days after V4. Participants may have vaginal intercourse (not required) during the use of IVR3 but should not have any other vaginal activity during the use of IVR3.
At V5 (For IVR only):
- IVR3 will be removed at this visit. Post IVR3 use vaginal swabs will be obtained in the clinic. Participants will be exited from the study at this visit or they may elect to use a different study product.
- Conditions
- HIV
- Being tested
- HEC Placebo gel, Placebo Intravaginal Ring, Placebo Vaginal Film, Placebo Vaginal Insert
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HEC Placebo gelOther
Placebo Intravaginal RingOther
Placebo Vaginal FilmOther
Placebo Vaginal InsertOther
| Study group | Role | What they receive |
|---|---|---|
| HEC Placebo Gel | Other | The placebo gel will come in pre-filled individual applicators (4mL). Placebo gel is clear in color and contains HEC as the gel thickener, purified water, sodium chloride, sorbic acid and sodium hydroxide. Receives: Other: HEC Placebo gel |
| Placebo Vaginal Insert | Other | The placebo vaginal inserts will be supplied in white plastic bottles. The placebo inserts are white to off-white in color, uncoated and bullet-shaped. The inserts are composed of ingredients generally recognized as safe including isomalt, xylitol, polyvinylpyrrolidone K 30, hydroxypropyl methylcellulose, poloxamer, and sodium stearyl fumarate. The inserts are approximately ½ to 1 inch long and approximately ¼ to ½ inch thick, similar in size to vaginal tablets that are currently available. Receives: Other: Placebo Vaginal Insert |
| Placebo Vaginal Film | Other | The placebo vaginal films will be individually wrapped. The placebo vaginal film is a thin, clear to translucent sheet with dimensions of 2 in x 2 in. The ingredients include hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC, E5), sodium carboxymethyl cellulose (NaCMC), and glycerin. Receives: Other: Placebo Vaginal Film |
| Placebo Intravaginal ring (IVR) | Other | The placebo IVRs will be supplied in individual foil pouches. Each ring has a longer white to off-white segment and a shorter transparent/translucent segment, and ingredients include polyurethane, glycerin, water and modified starch. Receives: Other: Placebo Intravaginal Ring |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence or absence of spectroscopic pattern signatures or other analytical methods measures of excipient or placebo products or vaginal bacteria in vaginal swabs
Measured: 1 - 7 days
Presence or absence of penetration of vaginally-derived biologic analytes or biofilms detected on returned IVRs
Measured: 1 - 7 days
Presence or absence of DNA (deoxyribonucleic acid) sequences of SRY (Sex-determining region in the Y chromosome) and TSPY4 (testis-specific protein Y-encoded)
Measured: 1 - 7 days
Presence or absence of amelogenin
Measured: 1 - 7 days
Changes in dimensions, weight, biologic or chemical composition of IVR
Assessments in dimensions, weight, biologic or chemical composition will be aggregated to inform changes in overall IVR characteristics
Measured: 1 day, 1 week, 1 month
Secondary outcomes (2)
Treatment-emergent adverse experiences among female participants per participant report: urogenital, product related, and/or serious
Measured: baseline and at 1 day, 1 week and 1 month
Changes on pelvic exam, as observed by the naked eye
Measured: baseline and at 1 day, 1 week and 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2015 (estimated)
- Study startOct 2015
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- 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
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02569697
- Sponsor's protocol ID
- D15-135
- Status last verified
- Sep 2016
- First submitted
- 21 Aug 2015
- Last updated
- 2 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of Adherence Biomarkers for Multiple Microbicide and Multipurpose Prevention Technology (MPT) Dosage Forms
- ClinicalTrials.gov ID
- NCT02569697
- Acronym / sponsor ID
- D15-135
- Conditions
- HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- CONRADUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 7 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to develop markers for use of placebo vaginal products and measure markers of mucosal semen exposure among healthy women. The study will also monitor safety of placebo product use.
Detailed description
This is a Phase I, non-randomized, open label study in healthy, non-pregnant, HIV negative women, who are not at risk of pregnancy, and are at low risk for STIs (sexually transmitted infections). Participants will be assigned to use one of four placebo products: IVR (intravaginal ring) (approximately 20 participants), and vaginal insert, film or HEC universal placebo gel (approximately 10 participants each). Each woman will provide pre-product use vaginal swabs. Participants assigned to vaginal insert, film or gel will use products with and without timed intercourse with their male partner for a total of two doses of the product, will provide vaginal swabs post product use, and will be seen over 4 visits.
Participants assigned to IVR do not have to be sexually active with a male partner. IVR assigned participants will use a total of 3 IVRs, one at a time. IVR assigned participants will use the first IVR (IVR1) for approximately 24 - 36 hours (no exposure to semen during IVR1 use). IVR assigned participants will use a second IVR (IVR2) for approximately 7 - 10 days and a third IVR (IVR3) for approximately 28 - 32 days. During the use of IVR2 and IVR3, participants may engage in sexual intercourse, but it is not required. Women assigned to IVR use will be seen over 5 visits.
Once a woman completes the study cycle with one study product, she may elect to do another cycle using a different product after a wash-out period of at least 7 days, if she can comply with study product specific protocol requirements. She may elect to do up to four cycles, each with a different study product. For each cycle, V1 screening procedures will be repeated as indicated by symptoms and or participant history, as assessed by the investigator and as outlined in the study manual. If re-screening procedures are not indicated, the new cycle may start with Visit 2 (V2).
At Visit 1 (V1), volunteers will be consented and undergo procedures to confirm they are eligible to continue in the study. Participants will be counseled to refrain from vaginal activity, as applicable, for 48 hours prior to V2.
V2 should occur on days 3 - 10 of the menstrual cycle, or for participants who do not have regular menstrual cycles, when the participant is not having heavy menstrual bleeding. Once it has been confirmed that the participant meets all of the inclusion criteria and none of the exclusion criteria, baseline pre-product use vaginal swabs will be taken. Participants will be required to refrain from any vaginal activity until after Visit 3 (V3).
- Participants assigned to gel, film or insert, will insert one dose (Dose 1) vaginally in the clinic. Vaginal swabs will be obtained in the clinic approximately 15 minutes after product use. Participants will be given vaginal swabs for home use. Participants will be instructed to obtain vaginal swabs, at bedtime daily, for 7 days, starting at the first bedtime after V2. Vaginal swabs will be stored in the participant's refrigerator and returned to the clinic at V3. V3 will occur 7 - 10 days after V2.
- For participants assigned to the IVR, the IVR1 will be inserted by the participant in the clinic. The participant will leave IVR1 in place until V3, which will occur 24 - 36 hours after V2.
At V3:
- Participants assigned to gel, film or insert will return used vaginal swabs to the clinic. Additional vaginal swabs will be obtained in the clinic. Participants will vaginally insert one dose of their assigned product (Dose 2) in the clinic. Vaginal swabs will be obtained in the clinic approximately 15 minutes after product use. The participants will be instructed to have vaginal intercourse with her male sexual partner within approximately 12 hours (± 4 hours) after insertion of the product. They will obtain vaginal swabs, at bedtime daily, for 7 days, starting at the first bedtime after V3 and after timed intercourse, as above. Participants will be instructed to refrain from additional acts of vaginal intercourse or other vaginal activity until Visit 4 (V4). Vaginal swabs will be stored in the participant's refrigerator and returned to the clinic at V4. V4 will occur 7 - 10 days after V3.
- For participants assigned to the IVR, IVR1 will be removed at this visit. Post IVR1 use vaginal swabs will be obtained in the clinic. The second IVR (IVR2) will be inserted by the participant in the clinic. The participant will be instructed to leave the IVR2 in place until V4, which will occur 7 - 10 days after V3. IVR Participants may have vaginal intercourse (not required) during the use of IVR2 but should not have any other vaginal activity during the use of IVR2.
At V4:
- Participants assigned to gel, film or insert will return used vaginal swabs to the clinic. Additional vaginal swabs will be obtained in the clinic. Participants will be exited from the study at this visit or they may elect to use a different study product.
- For participants assigned to the IVR, IVR2 will be removed at this visit. Post IVR2 use vaginal swabs will be obtained in the clinic. The third IVR (IVR3) will be inserted by the participant in the clinic. The participant will leave IVR3 in place until Visit 5 (V5), which will occur 28 - 32 days after V4. Participants may have vaginal intercourse (not required) during the use of IVR3 but should not have any other vaginal activity during the use of IVR3.
At V5 (For IVR only):
- IVR3 will be removed at this visit. Post IVR3 use vaginal swabs will be obtained in the clinic. Participants will be exited from the study at this visit or they may elect to use a different study product.
Study design
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HEC Placebo Gel | Other | Other: HEC Placebo gelThe placebo gel will come in pre-filled individual applicators (4mL). Placebo gel is clear in color and contains HEC as the gel thickener, purified water, sodium chloride, sorbic acid and sodium hydroxide. |
| Placebo Vaginal Insert | Other | Other: Placebo Vaginal InsertThe placebo vaginal inserts will be supplied in white plastic bottles. The placebo inserts are white to off-white in color, uncoated and bullet-shaped. The inserts are composed of ingredients generally recognized as safe including isomalt, xylitol, polyvinylpyrrolidone K 30, hydroxypropyl methylcellulose, poloxamer, and sodium stearyl fumarate. The inserts are approximately ½ to 1 inch long and approximately ¼ to ½ inch thick, similar in size to vaginal tablets that are currently available. |
| Placebo Vaginal Film | Other | Other: Placebo Vaginal FilmThe placebo vaginal films will be individually wrapped. The placebo vaginal film is a thin, clear to translucent sheet with dimensions of 2 in x 2 in. The ingredients include hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC, E5), sodium carboxymethyl cellulose (NaCMC), and glycerin. |
| Placebo Intravaginal ring (IVR) | Other | Other: Placebo Intravaginal RingThe placebo IVRs will be supplied in individual foil pouches. Each ring has a longer white to off-white segment and a shorter transparent/translucent segment, and ingredients include polyurethane, glycerin, water and modified starch. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
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 |
|---|---|---|
| HEC Placebo gel | Other | HEC Placebo Gel |
| Placebo Intravaginal Ring | Other | Placebo Intravaginal ring (IVR) |
| Placebo Vaginal Film | Other | Placebo Vaginal Film |
| Placebo Vaginal Insert | Other | Placebo Vaginal Insert |
Primary outcome
Presence or absence of spectroscopic pattern signatures or other analytical methods measures of excipient or placebo products or vaginal bacteria in vaginal swabs
Time frame: 1 - 7 days
Presence or absence of penetration of vaginally-derived biologic analytes or biofilms detected on returned IVRs
Time frame: 1 - 7 days
Presence or absence of DNA (deoxyribonucleic acid) sequences of SRY (Sex-determining region in the Y chromosome) and TSPY4 (testis-specific protein Y-encoded)
Time frame: 1 - 7 days
Presence or absence of amelogenin
Time frame: 1 - 7 days
Changes in dimensions, weight, biologic or chemical composition of IVR
Time frame: 1 day, 1 week, 1 month
Assessments in dimensions, weight, biologic or chemical composition will be aggregated to inform changes in overall IVR characteristics
2 secondary outcomes
Treatment-emergent adverse experiences among female participants per participant report: urogenital, product related, and/or serious
Time frame: baseline and at 1 day, 1 week and 1 month
Changes on pelvic exam, as observed by the naked eye
Time frame: baseline and at 1 day, 1 week and 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2016.
Related trials for HIV
Not yet recruitingPhase 1
huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
Enrolling by invitation
Evaluating the Efficacy of Annual CHTC Retesting Among Male Couples at High Risk of HIV Infection
HIV Infections
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Enrolling by invitation
Intervention to Reduce HIV Related Stigma Among Pregnant and Postpartum Women
HIV, HIV - Human Immunodeficiency Virus
Not yet recruitingPhase 4
Study of BIC/LEN FDC Versus Stable Baseline Regimens in Virologically Suppressed People With HIV
HIV-1 Infection
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of HIV, run by CONRAD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 2 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Presence or absence of spectroscopic pattern signatures or other analytical methods measures of excipient or placebo products or vaginal bacteria in vaginal swabs (time frame: 1 - 7 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Sep 2016.