Sitagliptin for implantatio

Phase 2

Completed

• Conditions: 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; Pregnancy and Childbirth; Recurrent miscarriage

• Registration Number: ISRCTN67932311
• Lead Sponsor: niversity Hospitals Coventry and Warwickshire NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-12-19
• Study Completion: 2017-08-31
• Last Update Posted: 29 June 2020

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 38

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The number of colonies per thousand endometrial stromal cells after three months of the IMP determined by a clonogenic assay.

Secondary Outcome Measures

Name	Time	Method
<br> 1. Change in the expression of DPP4 at the endometrium determined by immunohistochemistry<br> 2. RNA sequencing<br> 3. Methylation status of implantation related genes<br> 4. Adverse events/serious adverse events<br> 5. Acceptability of study determined by questionnaire<br> 6. Follow up pregnancy rates and outcomes<br>