Recurrent miscarriage
Conditions
Interventions
Trade Name: Januvia
Product Name: Sitagliptin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sitagliptin phosphate monohydrate
Sponsors
University Hospitals Coventry and Warwickshire NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Provision of informed written consent - History of recurrent miscarriage - 3 or more miscarriages, defined as three or more spontaneous pregnancy losses prior to 24 weeks gestation - Age 18-42 years at consent - Any BMI – no dose adjustment needed for BMI. BMI has no clinically meaningful effect on the pharmacokinetics of Sitagliptin. - Willing and able to give consent for the study and endometrial biopsy. - Ability to fully understand the requirements of the protocol - 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 - 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 - Negative pregnancy test on the day of randomisation Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - Under 18 years of age – the safety and effectiveness of Sitagliptin in paediatric patients under 18 has not yet been established. - Type I Diabetes – Sitagliptin should not be used in type 1 diabetes - Type II Diabetes – based on medical history - Pregnancy: tested at multiple points in trial – see schedule of events - Breast feeding – Caution is advised when prescribing Sitagliptin to breastfeeding mothers as it is not known if it is secreted in breast milk. - Known hypersensitivity to Sitagliptin - Not taking any medications with potential to react with the interventional product including Digoxin –plasma monitoring is needed if Sitagliptin used concomitantly in those at risk of digoxin toxicity, and Enalapril – Sitagliptin appears to alter the hypotensive effects of enalapril. - Previous diagnosis of pancreatitis - Renal impairment with eGFR<50 mL/min - 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) - Inclusion in another intervention trial - Unwilling to use effective contraception for the duration of the trial (from consent) - Allergy/sensitivity to excipients of the IMP/placebo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the effect of Sitagliptin on endometrial mesenchymal stem cell count. This will be assessed by the number of colonies per thousand endometrial stromal cells after 3 months of Sitagliptin (100mg) vs. 3 months of placebo, determined by a clonogenic assay.; Secondary Objective: The secondary objectives are to 1. To determine the effect of Sitagliptin on the expression of DPP4 at the endometrium. This will be assessed by looking at the change in the expression of DPP4 in the endometrium determined by immunohistochemistry. 2. To understand the effect of Sitagliptin administration on other implantation related genes. This will be assessed by RNA sequencing of endometrial mesenchymal stem cells and methylation status of implantation related genes after 3 months of Sitagliptin (100mg) vs. 3 months of placebo 4. To determine how well the IMP dosing schedule is tolerated by participants. This will be assessed by qualitative analysis of adverse events/serious adverse events reported in each treatment group (Sitagliptin vs. placebo). This analysis will include information collected onto the trial database at the 4 weekly follow up and also from a questionnaire given to them at the end of the trial. 5. To determine the acceptability of the protocol to study ; Primary end point(s): The number of colonies per thousand endometrial stromal cells after 3 months of 3 months of Sitagliptin (100mg) vs. 3 months of placebo, determined by a clonogenic assay. A standard operating procedure has been developed which describes in detail how the clonogenic assay is carried out. ; Timepoint(s) of evaluation of this end point: We will analyse endometrial biopsies as they are taken. The clonogenic assay takes a total of 12 days to complete. The last clonogenic assay from the | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To determine the effect of Sitagliptin on the expression of DPP4 at the endometrium We will measure the change in the expression of DPP4 in endometrial after 3 months of Sitagliptin (100mg) vs. 3 months of placebo determined by immunohistochemistry 2. To understand the effect of Sitagliptin administration on other implantation related genes We will do RNA sequencing of endometrial mesenchymal stem cells and methylation status of implantation related genes after 3 months of Sitagliptin (100mg) vs. 3 months of placebo 3. To determine how well the IMP dosing schedule is tolerated by participants We will do a qualitative analysis of adverse events/serious adverse events reported in each treatment group (Sitagliptin vs. placebo) 4. To determine the acceptability of the protocol to study participants We will do a qualitative analysis of process evaluation questionnaire in participants receiving IMP vs placebo. 5. Comparison of pregnancy rates and outcomes in participants receiving IMP vs. placebo ; Timepoint(s) of evaluation of this end point: Immunohistohemistry, RNA sequencing ad methylation status will be done as the biopsies are taken, Qualitative analyses of how well the IMP dosing schedule was tolerated and the acceptability of the study will be performed as soon as possible after the participant has their second endometrial biopsy. Pregnancy rates will be followed up for a total of 9 months after treatment. | — |
Countries
United Kingdom
Contacts
Public ContactDr Shreeya Tewary
University Hospitals Coventry and Warwickshire NHS Trust
Outcome results
None listed