The Use of Fish Oil Supplementation in Treatment of Intrahepatic Cholestasis of Pregnancy

Brief Title

The Use of Fish Oil Supplementation in Treatment of Intrahepatic Cholestasis of Pregnancy

Official Title

The Use of Fish Oil Supplementation in Treatment of Intrahepatic Cholestasis of Pregnancy

Brief Summary

      Intrahepatic cholestasis of pregnancy (ICP) is a unique disease of the liver resulting in
      abnormal bile acid levels and liver function. The incidence of ICP ranges from 0.1 - 15.6%.
      Women diagnosed with ICP most often present with itching, which may be severe. More
      concerning, however, is the impact of ICP on adverse fetal and pregnancy outcomes, including
      preterm delivery, meconium exposure, fetal demise, and increased neonatal respiratory
      complications. The risk for fetal demise has been estimated to be 1-3%. The mechanism of
      fetal demise in ICP is unknown, and therefore cannot be reliably predicted. There is evidence
      to suggest that extremely elevated bile acids levels are associated with worse fetal
      outcomes, particularly levels greater than 40 μmol/L.

      Ursodeoxycholic acid (UDCA) has anticholestatic effects, and is used to treat a variety of
      cholestatic liver diseases. Many studies have demonstrated superiority of UDCA over other
      agents, including dexamethasone and cholestyramine, for relief of maternal pruritus,
      improvement in transaminitis, reduction in serum bile acid concentrations, and improved
      pregnancy outcomes. As a result, UDCA is now widely used as first-line treatment for
      symptomatic relief in patients with ICP.

      Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two omega-3 long chain
      polyunsaturated fatty acids found in fish. DHA is known to play a key role in early fetal
      brain development, and has been associated with modest beneficial effects on
      neurodevelopmental and cognitive outcomes in children. In neonates with parental
      nutrition-induced cholestasis (PN-cholestasis), parental fish oil has been shown to be
      hepatoprotective not only for treatment of PN-cholestasis, but for prevention of cholestasis
      in premature infants at risk for the disease. Our hypothesis is that fish oil supplementation
      with DHA in women with ICP who are treated with UDCA will increase the rate of decline in
      serum total bile acid levels.

      The incidence of ICP at a single hospital center in Queens, NY is estimated to be 5%
      secondary to a high concentration of patients from high-risk ethnic groups. High risk
      patients with bile acid levels greater than or equal to 40 μmol/L are managed aggressively
      with inpatient admission for continuous fetal monitoring, treatment with UDCA, and serial
      total bile acid levels weekly. These are patients are routinely offered early delivery after
      documented fetal lung maturity between 36 and 37 weeks gestation, or for any signs of fetal
      distress. This study is a prospective randomized controlled trial comparing weekly serum
      total bile acid levels in women admitted for inpatient management of ICP among women
      supplemented with a standard prenatal vitamin versus supplementation with a prenatal vitamin
      and DHA.
    

Detailed Description

      Intrahepatic cholestasis of pregnancy (ICP) is a unique disease of the liver resulting in
      abnormal bile acid levels and liver function. In the literature, the incidence of ICP ranges
      from 0.1 - 15.6%.[1] Women diagnosed with ICP most often present with itching, which may be
      severe. More concerning, however, is the impact of ICP on adverse fetal and pregnancy
      outcomes, including preterm delivery, meconium exposure, fetal demise, and increased neonatal
      respiratory complications. The risk for fetal demise has been estimated to be 1-3%. The
      mechanism of fetal demise in ICP is unknown, and therefore cannot be reliably predicted.
      There is evidence to suggest that extremely elevated bile acids levels are associated with
      worse fetal outcomes, particularly levels greater than 40 μmol/L.[3] Ursodeoxycholic acid
      (UDCA) improves impaired hepatocellular secretion by stimulating canalicular bile acid
      transporter protein expression, and is now widely used as first-line treatment for
      symptomatic relief in patients with ICP. [1] Docosahexaenoic acid (DHA) and eicosapentaenoic
      acid (EPA) are two omega-3 long chain polyunsaturated fatty acids found in fish. DHA is known
      to play a key role in early fetal brain development, and has been associated with modest
      beneficial effects on neurodevelopmental and cognitive outcomes in children.[2] In neonates
      with parental nutrition-induced cholestasis (PN-cholestasis), parental fish oil has been
      shown to be hepatoprotective not only for treatment of PN-cholestasis, but for prevention of
      cholestasis in premature infants at risk for the disease.[3-5] The incidence of ICP at a
      single hospital center in Queens, NY is estimated to be 5% secondary to a high concentration
      of patients from high-risk ethnic groups. High risk patients with bile acid levels greater
      than or equal to 40 μmol/L are managed aggressively with inpatient admission for continuous
      fetal monitoring, treatment with UDCA, and serial total bile acid levels weekly, and are
      routinely offered early delivery after documented fetal lung maturity between 36 and 37 weeks
      gestation, or for any signs of fetal distress. This study is a prospective randomized trial
      of women diagnosed with ICP prior to 36 weeks who are admitted to Elmhurst Hospital for
      inpatient observation. Women will be randomized to receiving a standard prenatal vitamin
      daily or a prenatal vitamin plus fish oil supplementation in addition to the standard UDCA
      300mg by mouth three times daily. Dietary fish intake for each subject will be recorded.
      Total bile acid serum levels will be followed weekly, and fetal monitoring with daily
      non-stress tests will be performed on all women as per standard care for ICP at Elmhurst
      hospital. The primary outcome of interest is a 20% reduction in serum total bile acid levels
      in the treatment group compared to the control group at each time point. Secondary outcomes
      of interest include changes in maternal symptoms as measured using a validated itching score,
      changes in UDCA dosing, length of hospital stay, and neonatal outcomes including gestational
      age at delivery, Apgar scores, neonatal intensive care unit admissions, neonatal length of
      stay, meconium aspiration, birth weight, and perinatal mortality. Assuming 80% statistical
      power and a significance level of 0.05 to detect a 20% reduction in serum total bile acids in
      the treatment group compared to the placebo group, a total of 100 patients in each arm is
      needed.
    


Study Type

Interventional


Primary Outcome

Bile acid levels


Condition

Intrahepatic Cholestasis of Pregnancy

Intervention

Fish Oil Supplement Group

Study Arms / Comparison Groups

 Fish Oil Supplement Group
Description:  Receive the daily DHA pill and given a validated Itching Survey to assess maternal symptoms on admission and then weekly thereafter

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Dietary Supplement

Estimated Enrollment

0

Start Date

December 2012

Completion Date

May 2013

Primary Completion Date

May 2013

Eligibility Criteria

        Inclusion Criteria:

          -  All pregnant women aged 18 years or older admitted to Elmhurst Hospital Center (EHC)
             for inpatient management of ICP due to a serum total bile acid level > 40 μmol/L, or
             serum total bile acid level > 10 μmol/L with elevated AST or ALT, are eligible for
             enrollment

        Exclusion Criteria:

          -  Women < 18 years

          -  Women with allergies to fish
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Katherine Kohari, MD, , 



Administrative Informations


NCT ID

NCT01965054

Organization ID

GCO 12-1542


Responsible Party

Sponsor

Study Sponsor

Icahn School of Medicine at Mount Sinai


Study Sponsor

Katherine Kohari, MD, Principal Investigator, Icahn School of Medicine at Mount Sinai


Verification Date

October 2013