Sitagliptin for implantation
| ISRCTN | ISRCTN67932311 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN67932311 |
| EudraCT/CTIS number | 2016-001120-54 |
| Secondary identifying numbers | 31796 |
- Submission date
- 19/12/2016
- Registration date
- 19/12/2016
- Last edited
- 17/06/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Miscarriage is defined as the loss of pregnancy before 24 weeks of pregnancy and is the most common complication of pregnancy. 15-25% of pregnancies end in miscarriage, and between 25 and 50% of women will experience at least one miscarriage. Around 1% of all women experience recurrent miscarriage, where they experience several miscarriages in a row. Currently, the only effective treatment to prevent miscarriage is heparin and aspirin for those women with antiphospholipid syndrome (APLS). APLS is a disorder of the immune system that causes an increased risk of blood clots, and occurs in around 15% of women who experience recurrent miscarriage. However, there is no effective treatment for the 85% of recurrent miscarriage patients who do not also suffer from APLS. This study is based on new evidence that has shown that there is a strong association between recurrent miscarriage and a deficiency in stem cells at the endometrium (lining of the womb). The aim of this study is to find out if taking a medication called Sitagliptin, which has been shown in animal studies to increase the number of stem cells in other areas of the body in response to injury, can help increase the number of stem cells in the endometrium.
Who can participate?
Women who have experienced recurrent miscarriage
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive 100mg Sitagliptin and those in the second group receive a placebo (dummy pill). At the start of the study and then after three months, the stem cell count in the endometrium is measured and the lining of the womb is assessed to see if it has become more favourable for successful implantation.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
East Surrey Hospital (UK)
When is the study starting and how long is it expected to run for?
June 2016 to August 2017
Who is funding the study?
National Institute of Academic Anaesthesia (UK)
Who is the main contact?
Professor Siobhan Quenby
simplant@uhcw.nhs.uk
Contact information
Scientific
University Hospitals Coventry and Warwickshire NHS Trust
Clifford Bridge Road
Walsgrave
Coventry
CV2 2DX
United Kingdom
| Phone | +44 2476 964000 |
|---|---|
| simplant@uhcw.nhs.uk |
Study information
| Study design | Randomised; Interventional; Design type: Prevention, Drug, Cellular |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Does the DPP4 Inhibitor (Sitagliptin) Increase Endometrial Mesenchymal Stem Cells in Women with Recurrent Miscarriage? |
| Study acronym | SIMPLANT |
| Study objectives | The aim of this study is to assess whether Sitagliptin increases endometrial mesenchymal stem cells in women with repeated miscarriage compared to placebo. |
| Ethics approval(s) | South Central - Hampshire B Research Ethics Committee, 14/06/2016, ref: 16/SC/0229 |
| Health condition(s) or problem(s) studied | Specialty: Reproductive health and childbirth, Primary sub-specialty: Maternal/ Fetal medicine; UKCRC code/ Disease: Reproductive Health and Childbirth/ Other disorders originating in the perinatal period, Reproductive Health and Childbirth/ Fetus and newborn affected by maternal factors and by complications of pregnancy, labour and deliver |
| Intervention | Participants are randomised to receive 100mg sitagliptin or placebo. Participants are followed up after three months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Sitagliptin |
| Primary outcome measure | The number of colonies per thousand endometrial stromal cells after three months of the IMP determined by a clonogenic assay. |
| Secondary outcome measures | 1. Change in the expression of DPP4 at the endometrium determined by immunohistochemistry 2. RNA sequencing 3. Methylation status of implantation related genes 4. Adverse events/serious adverse events 5. Acceptability of study determined by questionnaire 6. Follow up pregnancy rates and outcomes |
| Overall study start date | 01/06/2016 |
| Completion date | 31/08/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 42 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 34; UK Sample Size: 34 |
| Total final enrolment | 38 |
| Key inclusion criteria | 1. Provision of informed written consent 2. History of recurrent miscarriage - 3 or more miscarriages (three or more spontaneous pregnancy losses prior to 24 weeks gestation) 3. Age 18-42 years at consent 4. Any BMI – no dose adjustment needed for BMI. BMI has no clinically meaningful effect on the pharmacokinetics of Sitagliptin. 5. Willing and able to give consent for the study and endometrial biopsy. 6. Ability to fully understand the requirements of the protocol 7. Adequate renal function , defined as Urea 2.5 – 7.8mmol/L, Creatinine 50 -90umol/L, potassium 3.5 – 5.3mmol/L, Sodium 133 -146mmol/L 8. Adequate hepatic function, defined as total protein 60 – 80g/L, Albumin 35-50g/L, Bilirubin 4-20umol/L, Alkaline Phosphatase (ALP) 35-105U/L, Alanine Transferase (ALT) 5-38 U/L 9. Negative pregnancy test on the day of randomisation |
| Key exclusion criteria | 1. Under 18 years of age – the safety and effectiveness of Sitagliptin in paediatric patients under 18 has not yet been established 2. Type I Diabetes – Sitagliptin should not be used in type 1 diabetes 3. Type II Diabetes – based on medical history 4. Pregnancy (tested at multiple points in trial) 5. Breast feeding – Caution is advised when prescribing Sitagliptin to breastfeeding mothers as it is not known if it is secreted in breast milk. 6. Known hypersensitivity to Sitagliptin 7. Not taking any medications with potential to react with interventional product: 7.1. Digoxin –plasma monitoring is needed if Sitagliptin used concomitantly in those at risk of digoxin toxicity 7.2. Enalapril – Sitagliptin appears to alter the hypotensive effects of enalapril 8. Previous diagnosis of pancreatitis 9. Renal impairment with eGFR<50 mL/min 10. Liver impairment, defined as any value out of normal range (total protein 60 – 80g/L, Albumin 35-50g/L, Bilirubin 4-20umol/L, Alkaline Phosphatase (ALP) 35-105U/L, Alanine Transferase (ALT) 5-38 U/L) 11. Inclusion in another intervention trial 12. Unwilling to use effective contraception for the duration of the trial (from consent) 13. Allergy/sensitivity to excipients of the IMP/placebo |
| Date of first enrolment | 14/09/2016 |
| Date of final enrolment | 01/06/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Walsgrave
Coventry
CV2 2DX
United Kingdom
Sponsor information
Hospital/treatment centre
Walsgrave General Hospital
Clifford Bridge Road
Coventry
CV2 2DX
England
United Kingdom
"ROR" |
https://ror.org/025n38288 |
|---|
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 17/06/2020 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
17/06/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
18/10/2017: Internal review.
