Preterm BirthPhase 1NCT05512052
Preventing Preterm Birth With a Negative Pressure Cervical Cup: a Feasibility Study
A Phase 1 study testing Hannah Cervical Cup (2 mm Delta), Hannah Cervical Cup (4 mm Delta) and Hannah Cervical Cup (6 mm Delta) in people with Preterm Birth and Cervical Incompetence, run by Galena Innovations, LLC at 1 site in United States.
Trial summary
The goal of this Phase I clinical trial is to generate proof-of-concept data to demonstrate that a cervical cup in combination with vacuum application will create negative pressure on uterine cervical tissue, thereby creating immediate cervical stiffness in order to prevent cervical ripening that is associated with… 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
- Preterm Birth, Cervical Incompetence, Cervical Insufficiency
- What is being tested?
- Hannah Cervical Cup (2 mm Delta), Hannah Cervical Cup (4 mm Delta) and Hannah Cervical Cup (6 mm Delta)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2023to Apr 2024
- 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
Who may be able to join
- women undergoing hysterectomy
Who cannot join
- if the candidate has undergone previous cervical surgeries or procedures including cerclage, loop electrosurgical excision procedure (LEEP), or cone biopsy
- has been diagnosed with collagen vascular disease
- a diagnosis of malignant or premalignant cervical changes
- a cervical length less than 15mm or greater than 45mm
- a cervical transverse diameter less than 15mm or greater than 35mm
Trial locations and contacts
1 site in 1 country.
United States1 site
Intermountain Utah Valley Hospital
Provo, Utah, 84604
Jake Krong
Helen Feltovich
About this study
The goal of this Phase I clinical trial is to generate proof-of-concept data to demonstrate that a cervical cup in combination with vacuum application will create negative pressure on uterine cervical tissue, thereby creating immediate cervical stiffness in order to prevent cervical ripening that is associated with spontaneous preterm birth.
Aim #1: Conduct a Phase I clinical study.
1A: Evaluate the ability of a cervical cup to improve cervical tissue physiology of uterine cervices in vivo for nonpregnant women.
1B: Evaluate the ability of a cervical cup to be safely placed and removed on uterine cervices in vivo for nonpregnant women.
Read the detailed description
Preterm birth (PTB), occurring at 20-36 weeks gestation, is a crisis. Out of 15M babies born preterm, 1.1M pass away yearly worldwide. Survivors face short- and long-term medical and neurodevelopmental complications. PTB contributes to long and frequent hospital stays. The World Health Organization (WHO) and the National Institute of Health (NIH) support initiatives that enable better care of maternal-infant dyad at risk for PTB. PTB costs the US $25B per year. Racial disparities (Black-14.39%, White-9.26%, and Hispanic-9.97%), suggest organizational and interpersonal biases.
All Spontaneous Preterm Birth (SPTB) results from early cervical change created by numerous biologic pathways causing contractions (preterm labor), lack of contractions (cervical insufficiency), or early amnion rupture (PPROM). Preterm labor, contractions leading to early cervical change, is experienced by 200,000 US women yearly resulting in PTB and PPROM affects 120,000 US mothers yearly. Cervical insufficiency, cervical change without contractions, has varied rates among reports. Current care (cerclage, progesterone, and tocolytics) centers on expectant rather than active management.
Cervical cerclage is a surgical procedure tying the cervix closed. Drawbacks include invasiveness, a tendency to tear through the cervix, the need for anesthesia during placement, and low rates of efficacy (18% for all types). Progesterone, a hormone given to prevent SPTB, is most strongly supported as a vaginal supplement, although this route isn't FDA approved. In 2003, it was recommended that IM hydroxyprogesterone caproate (17-OHPC) be given to women with a prior PTB to prevent SPTB. Following implementation, use hasn't shown benefit although it is still the only FDA approved medication. In 2019, the FDA motioned to begin removing 17-OHPC from the market. It is estimated that progesterone use lowers the risk of SPTB by only 0.01%. Tocolytics are medications used to prevent contractions and include magnesium sulfate, calcium channel blockers, betamimetics, and nonsteroidal anti-inflammatories (NSAIDs). Although tocolytics may, in some instances decrease preterm contractions, they have not been proven to be effective in preventing SPTB nor demonstrated improved neonatal outcomes. Tocolytic are associated with side effects, the most serious of which include fetal stroke, and maternal death. Tocolytics only temporarily address preterm contractions, cause harmful side effects, do not improve neonatal outcomes, and are ineffective at preventing SPTB.
No past interventions have effectively addressed early cervical change, even though premature cervical change is the commonality of all SPTB. Therefore, focusing on cervical change is the best place to concentrate in order to prevent SPTB, since it is the last step prior to birth.
Galena Innovations has created a medical device, the Hannah Cervical Cup, that addresses the unmet medical need in SPTB by focusing on preventing or reversing early cervical change. In every pregnancy, the cervix retains the fetus in the uterus and then allows delivery. The internal cervical os contracts closed with cervical stiffness. Through pregnancy, collagen breakdown crafts softening, enabling internal cervical os relaxation, leading to cervical change, which culminates in birth. However, in SPTB, this process happens earlier than is optimal. For those at risk for SPTB, the process of cervical softening can be prevented or reversed with an increase in cervical stiffness. The Hannah Cervical Cup is designed to improve cervical function both through an improvement in immediate cervical stiffness and long-term improvement in collagen function.
The goal of this Phase I project is to generate proof-of-concept data to establish that the Hannah Cervical Cup in combination with peristaltic vacuum pump application will safely create negative pressure on uterine cervical tissue, thereby creating immediate cervical stiffness in order to prevent cervical ripening that is associated with SPTB and to establish its feasibility as a treatment for SPTB. At the time of hysterectomy, prior to uterine removal, varying cup sizes will be applied to the cervix of 24-30 non-pregnant women with vacuum application over short-term exposures (10-15 minutes) and compared 8-10 control subjects.
- Being tested
- Hannah Cervical Cup (2 mm Delta), Hannah Cervical Cup (4 mm Delta), Hannah Cervical Cup (6 mm Delta)
- Keywords
- Cervix
- Medical subject headings
- Premature Birth, Uterine Cervical Incompetence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hannah Cervical Cup (2 mm Delta)Device
The Hannah Cervical Cup reverses and prevents early cervical change by improving cervical collagen function. It applies negative pressure to the cervix, placing it in a tensile strain. Collagen under tension elicits fibers to realign, creating initial stiffness. This enables the cervix to remain closed. Over time, the extracellular matrix becomes strengthened as tension increases collagen strength and synthesis, and decreases degradation and adhesions. It also decreases prostaglandins--inflammatory mediators that facilitate birth. The Hannah Cervical Cup will create stiffness and length in the cervix, provide a treatment for early rupture of fetal membranes, and will offer a mode of medication administration. It is simple in nature, non-invasive, may be used in low-income, low-resource settings, can be placed by a physician in inpatient and outpatient settings, and does not require anesthesia during placement. The Hannah Cervical Cup (2 mm Delta) displaces the cervical tissue by 2 mm.
Hannah Cervical Cup (4 mm Delta)Device
The Hannah Cervical Cup reverses and prevents early cervical change by improving cervical collagen function. It applies negative pressure to the cervix, placing it in a tensile strain. Collagen under tension elicits fibers to realign, creating initial stiffness. This enables the cervix to remain closed. Over time, the extracellular matrix becomes strengthened as tension increases collagen strength and synthesis, and decreases degradation and adhesions. It also decreases prostaglandins--inflammatory mediators that facilitate birth. The Hannah Cervical Cup will create stiffness and length in the cervix, provide a treatment for early rupture of fetal membranes, and will offer a mode of medication administration. It is simple in nature, non-invasive, may be used in low-income, low-resource settings, can be placed by a physician in inpatient and outpatient settings, and does not require anesthesia during placement. The Hannah Cervical Cup (4 mm Delta) displaces the cervical tissue by 4 mm.
Hannah Cervical Cup (6 mm Delta)Device
The Hannah Cervical Cup reverses and prevents early cervical change by improving cervical collagen function. It applies negative pressure to the cervix, placing it in a tensile strain. Collagen under tension elicits fibers to realign, creating initial stiffness. This enables the cervix to remain closed. Over time, the extracellular matrix becomes strengthened as tension increases collagen strength and synthesis, and decreases degradation and adhesions. It also decreases prostaglandins--inflammatory mediators that facilitate birth. The Hannah Cervical Cup will create stiffness and length in the cervix, provide a treatment for early rupture of fetal membranes, and will offer a mode of medication administration. It is simple in nature, non-invasive, may be used in low-income, low-resource settings, can be placed by a physician in inpatient and outpatient settings, and does not require anesthesia during placement. The Hannah Cervical Cup (6 mm Delta) displaces the cervical tissue by 6 mm.
| Study group | Role | What they receive |
|---|---|---|
| Hannah Cervical Cup (2 mm) | Experimental | Not described Receives: Device: Hannah Cervical Cup (2 mm Delta) |
| Hannah Cervical Cup (4 mm) | Experimental | Not described Receives: Device: Hannah Cervical Cup (4 mm Delta) |
| Hannah Cervical Cup (6 mm) | Experimental | Not described Receives: Device: Hannah Cervical Cup (6 mm Delta) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility: increases in cervical stiffness (in SWS m s-1) with cup and pressure application
Cervical stiffness with application of the cup and pressure combination ('cup SWS' measured in m s-1) will be measured and compared to cervical stiffness prior to application ('baseline SWS' measured in m s-1) to determine the significance of the change in stiffness.
Measured: 15-30 minutes
Secondary outcomes (1)
Safety: incidence (in number) of Treatment-Related Adverse Events
Measure the incidence (in number) of the following Treatment-Related Adverse Events:
- bleeding
- contusions
- infection
- abrasions
- tearing
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2022
- Study startApr 2023 (estimated)
- Primary completionApr 2024 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm BirthStudies 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
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Galena Innovations, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ashley C Crafton, Principal investigator, Galena Innovations
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05512052
- Sponsor's protocol ID
- 1A
- Status last verified
- Aug 2022
- First submitted
- 17 Aug 2022
- Last updated
- 26 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Preterm Birth With a Negative Pressure Cervical Cup: a Feasibility Study
- ClinicalTrials.gov ID
- NCT05512052
- Acronym / sponsor ID
- 1A
- Keywords
- Cervix
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Galena Innovations, LLCIndustry (pharma, biotech, devices)
- Study start
- Apr 2023 (estimated)
- Primary completion
- Apr 2024 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 23 Aug 2022 (actual)
- 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 goal of this Phase I clinical trial is to generate proof-of-concept data to demonstrate that a cervical cup in combination with vacuum application will create negative pressure on uterine cervical tissue, thereby creating immediate cervical stiffness in order to prevent cervical ripening that is associated with spontaneous preterm birth.
Aim #1: Conduct a Phase I clinical study.
1A: Evaluate the ability of a cervical cup to improve cervical tissue physiology of uterine cervices in vivo for nonpregnant women.
1B: Evaluate the ability of a cervical cup to be safely placed and removed on uterine cervices in vivo for nonpregnant women.
Detailed description
Preterm birth (PTB), occurring at 20-36 weeks gestation, is a crisis. Out of 15M babies born preterm, 1.1M pass away yearly worldwide. Survivors face short- and long-term medical and neurodevelopmental complications. PTB contributes to long and frequent hospital stays. The World Health Organization (WHO) and the National Institute of Health (NIH) support initiatives that enable better care of maternal-infant dyad at risk for PTB. PTB costs the US $25B per year. Racial disparities (Black-14.39%, White-9.26%, and Hispanic-9.97%), suggest organizational and interpersonal biases.
All Spontaneous Preterm Birth (SPTB) results from early cervical change created by numerous biologic pathways causing contractions (preterm labor), lack of contractions (cervical insufficiency), or early amnion rupture (PPROM). Preterm labor, contractions leading to early cervical change, is experienced by 200,000 US women yearly resulting in PTB and PPROM affects 120,000 US mothers yearly. Cervical insufficiency, cervical change without contractions, has varied rates among reports. Current care (cerclage, progesterone, and tocolytics) centers on expectant rather than active management.
Cervical cerclage is a surgical procedure tying the cervix closed. Drawbacks include invasiveness, a tendency to tear through the cervix, the need for anesthesia during placement, and low rates of efficacy (18% for all types). Progesterone, a hormone given to prevent SPTB, is most strongly supported as a vaginal supplement, although this route isn't FDA approved. In 2003, it was recommended that IM hydroxyprogesterone caproate (17-OHPC) be given to women with a prior PTB to prevent SPTB. Following implementation, use hasn't shown benefit although it is still the only FDA approved medication. In 2019, the FDA motioned to begin removing 17-OHPC from the market. It is estimated that progesterone use lowers the risk of SPTB by only 0.01%. Tocolytics are medications used to prevent contractions and include magnesium sulfate, calcium channel blockers, betamimetics, and nonsteroidal anti-inflammatories (NSAIDs). Although tocolytics may, in some instances decrease preterm contractions, they have not been proven to be effective in preventing SPTB nor demonstrated improved neonatal outcomes. Tocolytic are associated with side effects, the most serious of which include fetal stroke, and maternal death. Tocolytics only temporarily address preterm contractions, cause harmful side effects, do not improve neonatal outcomes, and are ineffective at preventing SPTB.
No past interventions have effectively addressed early cervical change, even though premature cervical change is the commonality of all SPTB. Therefore, focusing on cervical change is the best place to concentrate in order to prevent SPTB, since it is the last step prior to birth.
Galena Innovations has created a medical device, the Hannah Cervical Cup, that addresses the unmet medical need in SPTB by focusing on preventing or reversing early cervical change. In every pregnancy, the cervix retains the fetus in the uterus and then allows delivery. The internal cervical os contracts closed with cervical stiffness. Through pregnancy, collagen breakdown crafts softening, enabling internal cervical os relaxation, leading to cervical change, which culminates in birth. However, in SPTB, this process happens earlier than is optimal. For those at risk for SPTB, the process of cervical softening can be prevented or reversed with an increase in cervical stiffness. The Hannah Cervical Cup is designed to improve cervical function both through an improvement in immediate cervical stiffness and long-term improvement in collagen function.
The goal of this Phase I project is to generate proof-of-concept data to establish that the Hannah Cervical Cup in combination with peristaltic vacuum pump application will safely create negative pressure on uterine cervical tissue, thereby creating immediate cervical stiffness in order to prevent cervical ripening that is associated with SPTB and to establish its feasibility as a treatment for SPTB. At the time of hysterectomy, prior to uterine removal, varying cup sizes will be applied to the cervix of 24-30 non-pregnant women with vacuum application over short-term exposures (10-15 minutes) and compared 8-10 control subjects.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Hannah Cervical Cup (2 mm) | Experimental | Device: Hannah Cervical Cup (2 mm Delta) |
| Hannah Cervical Cup (4 mm) | Experimental | Device: Hannah Cervical Cup (4 mm Delta) |
| Hannah Cervical Cup (6 mm) | Experimental | Device: Hannah Cervical Cup (6 mm Delta) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- women undergoing hysterectomy
Key exclusion criteria (5 listed)
- if the candidate has undergone previous cervical surgeries or procedures including cerclage, loop electrosurgical excision procedure (LEEP), or cone biopsy
- has been diagnosed with collagen vascular disease
- a diagnosis of malignant or premalignant cervical changes
- a cervical length less than 15mm or greater than 45mm
- a cervical transverse diameter less than 15mm or greater than 35mm
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 |
|---|---|---|
| Hannah Cervical Cup (2 mm Delta)The Hannah Cervical Cup reverses and prevents early cervical change by improving cervical collagen function. It applies negative pressure to the cervix, placing it in a tensile strain. Collagen under tension elicits fibers to realign, creating initial stiffness. This enables the cervix to remain closed. Over time, the extracellular matrix becomes strengthened as tension increases collagen strength and synthesis, and decreases degradation and adhesions. It also decreases prostaglandins--inflammatory mediators that facilitate birth. The Hannah Cervical Cup will create stiffness and length in the cervix, provide a treatment for early rupture of fetal membranes, and will offer a mode of medication administration. It is simple in nature, non-invasive, may be used in low-income, low-resource settings, can be placed by a physician in inpatient and outpatient settings, and does not require anesthesia during placement. The Hannah Cervical Cup (2 mm Delta) displaces the cervical tissue by 2 mm. | Device | Hannah Cervical Cup (2 mm) |
| Hannah Cervical Cup (4 mm Delta)The Hannah Cervical Cup reverses and prevents early cervical change by improving cervical collagen function. It applies negative pressure to the cervix, placing it in a tensile strain. Collagen under tension elicits fibers to realign, creating initial stiffness. This enables the cervix to remain closed. Over time, the extracellular matrix becomes strengthened as tension increases collagen strength and synthesis, and decreases degradation and adhesions. It also decreases prostaglandins--inflammatory mediators that facilitate birth. The Hannah Cervical Cup will create stiffness and length in the cervix, provide a treatment for early rupture of fetal membranes, and will offer a mode of medication administration. It is simple in nature, non-invasive, may be used in low-income, low-resource settings, can be placed by a physician in inpatient and outpatient settings, and does not require anesthesia during placement. The Hannah Cervical Cup (4 mm Delta) displaces the cervical tissue by 4 mm. | Device | Hannah Cervical Cup (4 mm) |
| Hannah Cervical Cup (6 mm Delta)The Hannah Cervical Cup reverses and prevents early cervical change by improving cervical collagen function. It applies negative pressure to the cervix, placing it in a tensile strain. Collagen under tension elicits fibers to realign, creating initial stiffness. This enables the cervix to remain closed. Over time, the extracellular matrix becomes strengthened as tension increases collagen strength and synthesis, and decreases degradation and adhesions. It also decreases prostaglandins--inflammatory mediators that facilitate birth. The Hannah Cervical Cup will create stiffness and length in the cervix, provide a treatment for early rupture of fetal membranes, and will offer a mode of medication administration. It is simple in nature, non-invasive, may be used in low-income, low-resource settings, can be placed by a physician in inpatient and outpatient settings, and does not require anesthesia during placement. The Hannah Cervical Cup (6 mm Delta) displaces the cervical tissue by 6 mm. | Device | Hannah Cervical Cup (6 mm) |
Primary outcome
Feasibility: increases in cervical stiffness (in SWS m s-1) with cup and pressure application
Time frame: 15-30 minutes
Cervical stiffness with application of the cup and pressure combination ('cup SWS' measured in m s-1) will be measured and compared to cervical stiffness prior to application ('baseline SWS' measured in m s-1) to determine the significance of the change in stiffness.
1 secondary outcome
Safety: incidence (in number) of Treatment-Related Adverse Events
Time frame: 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2022.
- Individual participant dataSharing planned: No
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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.
Ashley C Crafton principal investigator
Galena Innovations
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 testing Hannah Cervical Cup (2 mm Delta), Hannah Cervical Cup (4 mm Delta) and Hannah Cervical Cup (6 mm Delta) in people with Preterm Birth and Cervical Incompetence, run by Galena Innovations, LLC 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?
The sponsor lists 1 inclusion and 5 exclusion criteria. 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: status not confirmed, as of the sponsor's last update on 26 Aug 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ashley C Crafton (208-870-0904, ashley@galenainnovations.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility: increases in cervical stiffness (in SWS m s-1) with cup and pressure application (time frame: 15-30 minutes). 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 26 Aug 2022.