PregnancyNCT02482363
Vascular Responses to UV Exposure in Pregnancy
A study testing UVA radiation in people with Pregnancy, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
Season of birth influences pregnancy for reasons that remain unclear however the answer may lie in the amount of sunshine pregnant women are exposed to. Sunshine, or ultraviolet light (UV) exposure is already known to have benefits for health on heart disease, strokes and depression. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pregnancy
- What is being tested?
- UVA radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2015to 31 Mar 2016
- Phase
- Interventional
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Pregnant volunteers
- Ages 18- - 45
- No significant medical or obstetric history
- English speaking
- Able to provide informed consent
- Singleton pregnancy
Show all 10Show fewer
- Low risk first trimester screen
- Have 4 hours of time
- Historical risk factors for growth restriction or pre-eclampsia
- Papp A < 0.40 MoMs
Who cannot join
- Non english speaking
- Smoking
- History of intrauterine growth restriction (IUGR) or pre-eclampsia
- BMI >40
- Contraindication to UV exposure
- History of blood born viruses (hepatitis B, C, HIV)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: UVA Irradiation of Skin in Pregnant Women Increases Uterine Artery Blood Flow and Reduces Blood Flow Through a Nitric Oxide Pathway
Season of birth influences pregnancy for reasons that remain unclear however the answer may lie in the amount of sunshine pregnant women are exposed to. Sunshine, or ultraviolet light (UV) exposure is already known to have benefits for health on heart disease, strokes and depression. In pregnancy, relationships between sunshine exposure are evident in birth weight, preterm birth and risk of blood pressure complications. Vitamin D, the UV generated hormone, was thought to be responsible when low vitamin D levels were associated with these pregnancy complications. However, vitamin D replacement is ineffective at preventing these outcomes, and the investigators hypothesise that this is because it is the UV that is beneficial for pregnancy and it is working through a different pathway.
A new understanding of skin function is central to this, with a 2014 study showing that exposing an adult to 20 minutes of low dose UV light lowered their blood pressure and improved blood flow. These investigators demonstrated this was a direct effect of UV on the skin and was mediated by nitric oxide, a chemical central to many aspects of pregnancy including blood pressure regulation and uterine activity.
Read more
The investigators in this study have funding from Tommy's to investigate if a similar effect is seen in pregnancy on the circulation. The design is similar to the previously successful method and volunteers would be recruited from clinical areas during the second trimester. As both resting and warming for 20 minutes have the potential to have similar effects on the circulation, a control arm will expose participants to these without the UV.
This pilot study would involve one visit and measurements taken would include heart rate, blood pressure, arteriography, ultrasound of the uterine arteries and blood measurements of nitric oxide levels. Arteriography is performed using a specialised arm cuff and is safe and non-invasive. A subset of these women would be invited to repeat this in the third trimester to investigate for a difference in effect at a later gestation.
Read the detailed description
The hypothesis is that ultraviolet A (UVA) exposure during pregnancy will release nitric oxide (NO) from the skin and that in turn this will cause blood vessel dilatation. This will be seen by changes in uterine artery blood flow, blood pressure, and arterial stiffness (arteriography). The aim is to investigate this in a low risk group and a high risk group, as these 2 groups of women have different baseline characteristics of their vascular system and potentially different responses to our intervention. A subset of these women will be invited to repeat the intervention in the third trimesters of their pregnancies to establish if the effect differs with advancing gestation. Birth outcomes on participants will be collected to check if the high and low risk groups are representative of this status.
Participant contact information will be kept separately from their collected data to anonymise the collected data and all outcome data will be de-identified. All collected information will be stored on secure university servers that are password protected.
Participants will be recruited to participate in the low sunshine months November 1st until March 1st to minimise background sunshine and UV exposure.
LOW RISK ARM:
20 participants will be recruited from community and hospital antenatal clinics, day assessment unit, labour ward or at first trimester screen appointment by posters, a research midwife or a member of clinical research team. Potential participants will be given an information form and will be asked to give written consent following sufficient time for consideration.
The participants will be between 14 and 28 weeks pregnant at the time of the intervention and have no pregnancy related complications or risk factors for pre-eclampsia or growth restriction.
Over a single morning or afternoon the protocol will be completed with the participant exposed to both the intervention and the control in the one 4 hour period. The intervention participants will be exposed to is ultraviolet A for 20minutes in a dermatology phototherapy cabinet. This is the equivalent of 2 standard erythemal doses (SED's) of UV light exposure. On a normal summer day in Northern Europe the general population would expect to receive 30-40 SED's. In the control intervention participants will be exposed to sham irradiation where they will undergo this exposure while wearing a loose fitting paper boiler suit that is UVA impenetrable to prevent UVA exposure. Protective sunglasses will be provided.
On arrival at the Wellcome Trust Clinical Research Facility, participants will be randomized to the active or control treatment arm first with a simple randomisation method (coin toss) by a member of the clinical research team. As the groups will be controlled for risk factors, the main important covariate is age. The purpose of randomisation in this setting is to aid with blinding the ultrasound investigator to which arm the patient is in, as the investigator can affect ultrasound results. As such, a simple randomisation procedure such as a coin toss by the research nurse on arrival is appropriate. One toss will determine group allocation with heads getting control exposure first and tails getting intervention first. This will be recorded on the participant information sheet and unblinded for analysis. The participant will then rest seated for 30 minutes in comfortable clothing in a temperature controlled room at 25 degrees Celsius. They will be assigned a study number and the researcher will collect pregnancy and maternal characteristics.
A member of the research team will measure baseline blood pressure, skin temperature, heart rate and perform arteriography. Arteriography has a standard collecting procedure and is an established tool to measure stiffness of the aorta (the largest blood vessel from the heart). An ultrasound will confirm fetal viability and baseline uterine artery Doppler measurements. An intravenous (IV) cannula will be inserted and a 5ml venous blood sample will be collected by an experienced member of the clinical research team.
The participant will then be exposed to the intervention of UVA for 20 minutes in either their underwear (active) or in a loose fitting paper boiler suit that is UVA impenetrable. The suit allows the skin to heat up, but not be exposed to the UVA. This controls for any temperature effects. The investigator performing ultrasound is blinded to whether the participant was wearing the suit or not by the use of a research nurse and the investigator not being present during the irradiation.
Immediately following exposure BP, heart rate, skin temperature and uterine artery Doppler's will be measured at 10 minutely intervals for 1 hour. 3 measurements will be collected at each time point for BP, heart rate and uterine artery Doppler. A venous blood sample will be collected from the cannula at the 0, 30 and 60 minute time points. At the 60 minute time point, arteriography will be repeated. Uterine artery Doppler images will be stored with a study number for offline analysis.
The participant will then cross over in to the other arm, which the investigator remains blind to and the process is repeated.
HIGH RISK ARM:
20 participants between 14 and 28 weeks will be referred from their direct care team based on historical risk factors in a previous pregnancy or high risk factors in their current pregnancy including essential hypertension, renal or vascular disease, previous intrauterine growth restriction or from a low Papp-A result on their first trimester screening blood tests. Papp-A is measured as part of first trimester screening and is produced by the developing placenta. Low results are associated with poor fetal growth and pre-eclampsia. Their direct care team in community or hospital antenatal clinics, day assessment unit or in the ultrasound department may identify these potential participants and refer them to the research team if they are interested in participating. This will include midwives, doctors and ultrasound staff. A poster and mechanism for self referral will be present in the care areas of antenatal clinic and the ultrasound department. If they give consent, they will be recruited to participate. If there is any concerns about fetal or maternal well being they will be excluded from this trial.
They will undergo the above protocol including randomisation.
LONGITUDINAL ARM:
All participants will be invited to return to undergo the trial protocol again at a third trimester time point within the 3 month window that the trial is being run. The investigators would aim to collect 10 from the low risk group and 10 from the high risk group. Participants whose third trimester commences outside this window will not be eligible for the longitudinal group.
FOR ALL GROUPS:
The consent will include permission to collect birth outcomes once they are delivered. Outcomes of interest will be pregnancy outcome (stillbirth, live birth), birth weight, gestational length, incidence of pre-eclampsia or pregnancy induced hypertension. This will be retrieved from the medical record and will be used for post hoc subgroup analysis to assess for any difference in response to UVA exposure. The study will conclude once the last baby is delivered and their birth data collected.
Results will be recorded in an anonymised way with a study number, and anonymised data will be stored separately to participant data. After the last pregnancy is delivered, all data will be completely de-identified. Blood samples will be stored in the Edinburgh Reproductive Tissue Biobank with participant consent.
- Conditions
- Pregnancy
- Being tested
- UVA radiation, Sham Control
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UVA radiationRadiation
20 minutes of low dose UVA from a phototherapy unit
Sham ControlRadiation
20 minutes of sham control exposure
| Study group | Role | What they receive |
|---|---|---|
| Active UVA radiation | Active comparator | This arm will receive 20 minutes of UVA to the skin while resting quietly. Receives: Radiation: UVA radiation |
| Sham control | Sham comparator | This arm will receive 20 minutes of quiet rest and heat but with their skin protected from UVA Receives: Radiation: Sham Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Uterine artery Doppler
The uterine artery will be interrogated with abdominal ultrasound to determine diameter and Doppler measurements to calculate resistance indices (PI) and flow velocity. This will be done at baseline and at 10 minutely intervals following exposure for 60 minutes.
Measured: Change over 60 minutes following exposure
Secondary outcomes (3)
Blood pressure
Blood pressure will be measured with an appropriate sized cuff to determine blood pressure at baseline and the at ten minutely intervals following exposure.
Measured: 60 minutes
Nitrospecies
Nitrate and nitrite levels will be measured in the venous circulation at baseline. These are metabolites of nitric oxide metabolism.
Measured: 60 minutes
Arteriography
Arteriography is a measurement that reflects changes in air
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2015 (estimated)
- Study start1 Sep 2015
- Primary completion31 Mar 2016
- Study completion31 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PregnancyStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- SARAH STOCK, BSc MBChB, Principal investigator, QUEEN'S MEDICAL RESEARCH INSTITUTE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02482363
- Sponsor's protocol ID
- 170108
- Status last verified
- May 2024
- First submitted
- 12 Jun 2015
- Last updated
- 21 May 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- UVA Irradiation of Skin in Pregnant Women Increases Uterine Artery Blood Flow and Reduces Blood Flow Through a Nitric Oxide Pathway
- ClinicalTrials.gov ID
- NCT02482363
- Acronym / sponsor ID
- 170108
- Conditions
- Pregnancy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- 1 Sep 2015 (actual)
- Primary completion
- 31 Mar 2016 (actual)
- Study completion
- 31 Mar 2016 (actual)
- First posted
- 26 Jun 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.
Season of birth influences pregnancy for reasons that remain unclear however the answer may lie in the amount of sunshine pregnant women are exposed to. Sunshine, or ultraviolet light (UV) exposure is already known to have benefits for health on heart disease, strokes and depression. In pregnancy, relationships between sunshine exposure are evident in birth weight, preterm birth and risk of blood pressure complications. Vitamin D, the UV generated hormone, was thought to be responsible when low vitamin D levels were associated with these pregnancy complications. However, vitamin D replacement is ineffective at preventing these outcomes, and the investigators hypothesise that this is because it is the UV that is beneficial for pregnancy and it is working through a different pathway.
A new understanding of skin function is central to this, with a 2014 study showing that exposing an adult to 20 minutes of low dose UV light lowered their blood pressure and improved blood flow. These investigators demonstrated this was a direct effect of UV on the skin and was mediated by nitric oxide, a chemical central to many aspects of pregnancy including blood pressure regulation and uterine activity.
The investigators in this study have funding from Tommy's to investigate if a similar effect is seen in pregnancy on the circulation. The design is similar to the previously successful method and volunteers would be recruited from clinical areas during the second trimester. As both resting and warming for 20 minutes have the potential to have similar effects on the circulation, a control arm will expose participants to these without the UV.
This pilot study would involve one visit and measurements taken would include heart rate, blood pressure, arteriography, ultrasound of the uterine arteries and blood measurements of nitric oxide levels. Arteriography is performed using a specialised arm cuff and is safe and non-invasive. A subset of these women would be invited to repeat this in the third trimester to investigate for a difference in effect at a later gestation.
Detailed description
The hypothesis is that ultraviolet A (UVA) exposure during pregnancy will release nitric oxide (NO) from the skin and that in turn this will cause blood vessel dilatation. This will be seen by changes in uterine artery blood flow, blood pressure, and arterial stiffness (arteriography). The aim is to investigate this in a low risk group and a high risk group, as these 2 groups of women have different baseline characteristics of their vascular system and potentially different responses to our intervention. A subset of these women will be invited to repeat the intervention in the third trimesters of their pregnancies to establish if the effect differs with advancing gestation. Birth outcomes on participants will be collected to check if the high and low risk groups are representative of this status.
Participant contact information will be kept separately from their collected data to anonymise the collected data and all outcome data will be de-identified. All collected information will be stored on secure university servers that are password protected.
Participants will be recruited to participate in the low sunshine months November 1st until March 1st to minimise background sunshine and UV exposure.
LOW RISK ARM:
20 participants will be recruited from community and hospital antenatal clinics, day assessment unit, labour ward or at first trimester screen appointment by posters, a research midwife or a member of clinical research team. Potential participants will be given an information form and will be asked to give written consent following sufficient time for consideration.
The participants will be between 14 and 28 weeks pregnant at the time of the intervention and have no pregnancy related complications or risk factors for pre-eclampsia or growth restriction.
Over a single morning or afternoon the protocol will be completed with the participant exposed to both the intervention and the control in the one 4 hour period. The intervention participants will be exposed to is ultraviolet A for 20minutes in a dermatology phototherapy cabinet. This is the equivalent of 2 standard erythemal doses (SED's) of UV light exposure. On a normal summer day in Northern Europe the general population would expect to receive 30-40 SED's. In the control intervention participants will be exposed to sham irradiation where they will undergo this exposure while wearing a loose fitting paper boiler suit that is UVA impenetrable to prevent UVA exposure. Protective sunglasses will be provided.
On arrival at the Wellcome Trust Clinical Research Facility, participants will be randomized to the active or control treatment arm first with a simple randomisation method (coin toss) by a member of the clinical research team. As the groups will be controlled for risk factors, the main important covariate is age. The purpose of randomisation in this setting is to aid with blinding the ultrasound investigator to which arm the patient is in, as the investigator can affect ultrasound results. As such, a simple randomisation procedure such as a coin toss by the research nurse on arrival is appropriate. One toss will determine group allocation with heads getting control exposure first and tails getting intervention first. This will be recorded on the participant information sheet and unblinded for analysis. The participant will then rest seated for 30 minutes in comfortable clothing in a temperature controlled room at 25 degrees Celsius. They will be assigned a study number and the researcher will collect pregnancy and maternal characteristics.
A member of the research team will measure baseline blood pressure, skin temperature, heart rate and perform arteriography. Arteriography has a standard collecting procedure and is an established tool to measure stiffness of the aorta (the largest blood vessel from the heart). An ultrasound will confirm fetal viability and baseline uterine artery Doppler measurements. An intravenous (IV) cannula will be inserted and a 5ml venous blood sample will be collected by an experienced member of the clinical research team.
The participant will then be exposed to the intervention of UVA for 20 minutes in either their underwear (active) or in a loose fitting paper boiler suit that is UVA impenetrable. The suit allows the skin to heat up, but not be exposed to the UVA. This controls for any temperature effects. The investigator performing ultrasound is blinded to whether the participant was wearing the suit or not by the use of a research nurse and the investigator not being present during the irradiation.
Immediately following exposure BP, heart rate, skin temperature and uterine artery Doppler's will be measured at 10 minutely intervals for 1 hour. 3 measurements will be collected at each time point for BP, heart rate and uterine artery Doppler. A venous blood sample will be collected from the cannula at the 0, 30 and 60 minute time points. At the 60 minute time point, arteriography will be repeated. Uterine artery Doppler images will be stored with a study number for offline analysis.
The participant will then cross over in to the other arm, which the investigator remains blind to and the process is repeated.
HIGH RISK ARM:
20 participants between 14 and 28 weeks will be referred from their direct care team based on historical risk factors in a previous pregnancy or high risk factors in their current pregnancy including essential hypertension, renal or vascular disease, previous intrauterine growth restriction or from a low Papp-A result on their first trimester screening blood tests. Papp-A is measured as part of first trimester screening and is produced by the developing placenta. Low results are associated with poor fetal growth and pre-eclampsia. Their direct care team in community or hospital antenatal clinics, day assessment unit or in the ultrasound department may identify these potential participants and refer them to the research team if they are interested in participating. This will include midwives, doctors and ultrasound staff. A poster and mechanism for self referral will be present in the care areas of antenatal clinic and the ultrasound department. If they give consent, they will be recruited to participate. If there is any concerns about fetal or maternal well being they will be excluded from this trial.
They will undergo the above protocol including randomisation.
LONGITUDINAL ARM:
All participants will be invited to return to undergo the trial protocol again at a third trimester time point within the 3 month window that the trial is being run. The investigators would aim to collect 10 from the low risk group and 10 from the high risk group. Participants whose third trimester commences outside this window will not be eligible for the longitudinal group.
FOR ALL GROUPS:
The consent will include permission to collect birth outcomes once they are delivered. Outcomes of interest will be pregnancy outcome (stillbirth, live birth), birth weight, gestational length, incidence of pre-eclampsia or pregnancy induced hypertension. This will be retrieved from the medical record and will be used for post hoc subgroup analysis to assess for any difference in response to UVA exposure. The study will conclude once the last baby is delivered and their birth data collected.
Results will be recorded in an anonymised way with a study number, and anonymised data will be stored separately to participant data. After the last pregnancy is delivered, all data will be completely de-identified. Blood samples will be stored in the Edinburgh Reproductive Tissue Biobank with participant consent.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active UVA radiation | Active comparator | Radiation: UVA radiationThis arm will receive 20 minutes of UVA to the skin while resting quietly. |
| Sham control | Sham comparator | Radiation: Sham ControlThis arm will receive 20 minutes of quiet rest and heat but with their skin protected from UVA |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Pregnant volunteers
- Ages 18- - 45
- No significant medical or obstetric history
- English speaking
- Able to provide informed consent
Key exclusion criteria (6 listed)
- Non english speaking
- Smoking
- History of intrauterine growth restriction (IUGR) or pre-eclampsia
- BMI >40
- Contraindication to UV exposure
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 |
|---|---|---|
| UVA radiation20 minutes of low dose UVA from a phototherapy unit | Radiation | Active UVA radiation |
| Sham Control20 minutes of sham control exposure | Radiation | Sham control |
Primary outcome
Uterine artery Doppler
Time frame: Change over 60 minutes following exposure
The uterine artery will be interrogated with abdominal ultrasound to determine diameter and Doppler measurements to calculate resistance indices (PI) and flow velocity. This will be done at baseline and at 10 minutely intervals following exposure for 60 minutes.
3 secondary outcomes
Blood pressure
Time frame: 60 minutes
Nitrospecies
Time frame: 60 minutes
Arteriography
Time frame: 60 minutes
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 21 May 2024.
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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.
SARAH STOCK, BSc MBChB principal investigator
QUEEN'S MEDICAL RESEARCH INSTITUTE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing UVA radiation in people with Pregnancy, run by University of Edinburgh at 1 site in United Kingdom.
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 10 inclusion and 6 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: finished, as of the sponsor's last update on 21 May 2024. 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 Kingdom. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Uterine artery Doppler (time frame: Change over 60 minutes following exposure). 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 21 May 2024; AzTrials last refreshed its copy on 6 Nov 2026.