Metformin in Intrahepatic Cholestasis of Pregnancy

Phase 2

• Conditions: Pregnancy Complications; Intrahepatic Cholestases
• Interventions: Drug: Ursodeoxycholic Acid; Drug: Metformin

• Registration Number: NCT03056274
• Lead Sponsor: Epsom and St Helier University Hospitals NHS Trust

Brief Summary

This is a pilot study aimed at comparing the effect of metformin versus ursodeoxycholic acid in women with intrahepatic cholestasis in pregnancy. The study will be conducted in three NHS hospital sites, over an 18 month period.

Detailed Description

Intrahepatic cholestasis is a condition that affects pregnant women. It is characterised by itching, usually in the third trimester of pregnancy and is associated with an increase in the liver enzymes and bile salts. This can be associated with maternal and neonatal morbidity, and rarely perinatal mortality.

The investigators propose to assess and compare the effect of Metformin versus Ursodeoxycholic acid on lowering liver enzymes and bile salts, improving maternal morbidity and improving neonatal outcomes.

This study is a pilot study that will be conducted at 3 NHS hospital sites where patients will randomly assigned to receive either Metformin or Ursodeoxycholic acid. There will be 20 patient in each arm. Recruitment will commence in February 2017 and will run for an 18 month period.

Study Timeline

• Study First Submitted: 2016-12-22
• Study First Submitted QC: 2017-02-14
• Study First Posted: 2017-02-17
• Status Verified: 2018-01
• Last Update Submitted: 2018-07-24
• Last Update Posted: 2018-07-26
• Study Start: 2019-01
• Primary Completion: 2019-06
• Study Completion: 2019-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

1. 20+0 to 40 weeks' gestation on day of randomisation
2. Itching with a raised serum bile acid above the upper limit of normal
3. Normal anomaly scan at 20 weeks
4. Aged 18 years or over
5. Able to give written informed consent
6. No known pre-existing liver disease

Exclusion Criteria

1. Decision already made for delivery within the next 48 hours
2. Known allergy to any component of the ursodeoxycholic acid or metformin tablets
3. Patients already on metformin for other conditions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin arm	Ursodeoxycholic Acid	Metformin
Ursodeoxycholic acid	Metformin	Ursodeoxycholic acid

Primary Outcome Measures

Name	Time	Method
Normalisation of maternal serum concentration of bile salts and liver enzymes	From date of randomisation to date of delivery assessed up to 26 weeks	Normalisation of Bile acids and liver enzymes - both parameters are the cornerstone for a diagnosis of intrahepatic cholestasis. They have been separated into two outcomes due to to the different laboratory indices of measurement. Results will be aggregated together to report number of patients with abnormal results
Normalisation of maternal serum concentration of liver enzymes	From date of randomisation to date of delivery assessed up to 26 weeks	Normalisation of liver enzymes Alanine transaminase Aspartate transaminase Bilirubin (total) Gamma glutamyl transferase Results will be aggregated together to report the number of patients with abnormal liver enzymes

Secondary Outcome Measures

Name	Time	Method
Fetal outcomes	Immediately upon delivery date	Gestational age at delivery