Condition category
Pregnancy and Childbirth
Date applied
19/12/2016
Date assigned
19/12/2016
Last edited
19/12/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Siobhan Quenby

ORCID ID

Contact details

University Hospitals Coventry and Warwickshire NHS Trust
Clifford Bridge Road
Walsgrave
Coventry
CV2 2DX
United Kingdom
+44 2476 964000
simplant@uhcw.nhs.uk

Additional identifiers

EudraCT number

2016-001120-54

ClinicalTrials.gov number

Protocol/serial number

31796

Study information

Scientific title

Does the DPP4 Inhibitor (Sitagliptin) Increase Endometrial Mesenchymal Stem Cells in Women with Recurrent Miscarriage?

Acronym

SIMPLANT

Study hypothesis

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

South Central - Hampshire B Research Ethics Committee, 14/06/2016, ref: 16/SC/0229

Study design

Randomised; Interventional; Design type: Prevention, Drug, Cellular

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Phase

Phase II

Drug names

Sitagliptin

Primary outcome measures

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 trial start date

01/06/2016

Overall trial end date

31/08/2017

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 34; UK Sample Size: 34

Participant 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

Recruitment start date

14/09/2016

Recruitment end date

01/06/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospitals Coventry and Warwickshire NHS Trust
Clifford Bridge Road Walsgrave
Coventry
CV2 2DX
United Kingdom

Sponsor information

Organisation

University Hospitals Coventry and Warwickshire NHS Trust

Sponsor details

Walsgrave General Hospital
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Tommy's Baby Charity

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes