Official Title: “S. Japonicum and Pregnancy Outcomes: A Randomized, Double Blind, Placebo Controlled Trial (RCT)”

This study will look at the safety and effectiveness of praziquantel (PZQ), a medication to treat schistosomiasis (a type of worm) infection, among pregnant women and their unborn babies living in Leyte, The Philippines. It is thought that PZQ is safe and effective in treating Schistosomiasis in pregnant women. Five hundred infected pregnant women ages 18 and over will participate. Study volunteers 12-16 weeks pregnant will be given PZQ or a pill without any medicine (placebo) and stay in the hospital overnight. Small blood samples will be collected before and after the medication is taken. Three stool and urine samples will be taken during a total of 7 study visits. An ultrasound image (picture or outline of the unborn baby) will be looked at by placing a probe on the mother's lower stomach. When the baby is born, a small blood sample will be taken. Mother and baby will be followed for up to 8 months before the baby is born and 1 month after.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2011

This double-blind, placebo-controlled study will investigate praziquantel (PZQ) for treatment of Schistosomiasis japonicum in pregnant women living in endemic villages of Leyte, The Philippines. The study will enroll 500 pregnant women, ages 18 and over, infected with S.

japonicum. The primary study objective is to quantify the efficacy of PZQ treatment for S.

japonicum at 12-16 weeks gestation on newborn birth weight among live births. This will be assessed by measuring birth weight within 96 hours of delivery to 10 grams. The 1st secondary objective is to assess treatment efficacy with respect to maternal and newborn nutritional status and maternal parasitologic response to treatment. This will be assessed by: evaluating maternal iron status (ferritin and serum transferrin receptor) and hemoglobin at 32 weeks gestation; change in maternal nutritional status from first trimester to 32 week visit; newborn iron stores as assessed by cord blood ferritin and hemoglobin; and parasitologic response to treatment reported as percent reduction in egg counts from the mean S. japonicum eggs per gram of stool at screening to the mean S. japonicum eggs per gram of stool at 22 weeks gestation. "Successful" treatment will be defined as a 90% or greater reduction in egg counts from pre-treatment to 22 weeks gestation. The 2nd secondary objective is to collect preliminary safety and toxicity data on use of PZQ among pregnant women and their newborns.

This will be assessed by evaluating: incidence of maternal convulsion after PZQ dosing; toxicity to maternal bone marrow, kidney, and liver as measured by laboratory parameters collected just before, and 24-48 hours after dose; immediate toxicity to the fetus as assessed by abortion (fetal demise before 20 weeks gestation); and long-term toxicity to the fetus as assessed by rates of pre-maturity measured by modified Dubowitz exam at delivery, low-birth weight, stillbirth as defined by fetal demise after 20 weeks gestation, and congenital anomalies as determined by physical exam performed by a pediatrician at 28 days of life. The 3rd secondary objective is to identify extra-placental mechanisms mediating the hypothesized beneficial effect of PZQ on birth outcomes. The hypothesized mechanisms include:

improved maternal iron bio-availability for transfer to the developing fetus and improved maternal nutritional status as assessed by anthropometric measures of body size. The 4th secondary objective is to identify extra-placental mechanisms mediating the hypothesized beneficial effect of PZQ on birth outcomes. The hypothesized mechanisms include: decreased concentrations of TNF-alpha, IFN-gamma, and IL-6 and increased concentrations of IL-10 compared in placental blood from S. japonicum infected, PZQ treated mothers compared to untreated mothers; decreased secretion of TNF-alpha, IFN-gamma, and IL-6 and more IL-10 secretion from placental explants from S. japonicum infected, PZQ treated women when stimulated with soluble parasite egg antigen compared to placental explants from S. japonicum infected, PZQ untreated mothers; and lower level of apoptosis in cultured trophoblasts exposed to peripheral serum as measured by cytokeratin 18 neo-epitope staining among S.

japonicum infected, PZQ treated mothers versus untreated mothers. Participants will be involved in study related procedures for 9 months (8 months pre-natally and 1 month post-natally) for mother and infant.

Intervention(s) in this Clinical Trial

• Drug: Placebo
  • Inert compound dextrose, gel encapsulation.
• Drug: Praziquantel
  • 60 mg/kg PO given in split dose (30/mg/kg each) separated by at least 3 hours; gel encapsulated with 2 different color capsules.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
  • Placebo at 12-16 weeks gestation
• Experimental: 2
  • A single therapeutic dose of PZQ at 12-16 weeks gestation

Primary Measures

• Newborn birth weight.
  • Time Frame: Within 24 hours of delivery.
    Safety Issue?: No

Secondary Measures

• Efficacy: maternal hemoglobin and iron status, assessment of anemia of inflammation.
  • Time Frame: Hemoglobin will be measured at 14 (+/- 2) weeks and 32 weeks.
    Safety Issue?: No
• Newborn hemoglobin and iron status.
  • Time Frame: At 2-6 days of life.
    Safety Issue?: Yes
• Maternal weight gain.
  • Time Frame: At enrollment and a second weight obtained at 32 weeks.
    Safety Issue?: Yes
• Parasitological response to treatment.
  • Time Frame: Measured at 22 weeks gestation.
    Safety Issue?: Yes
• Identification of placental mechanisms mediating improved outcomes in the PZQ group.
  • Time Frame: At delivery.
    Safety Issue?: No
• Identification of extra-placental mechanisms mediating improved outcomes in the PZQ group.
  • Time Frame: 32 weeks.
    Safety Issue?: Yes
• Pre-eclampsia.
  • Time Frame: 22 weeks and 32 weeks.
    Safety Issue?: Yes
• Newborn congenital anomalies.
  • Time Frame: Delivery, within 2-6 days of delivery, and 28 days of life.
    Safety Issue?: Yes
• PZQ toxicology.
  • Time Frame: 12-16 weeks gestation (baseline) and 24 hours after the dose and before discharge from the hospital.
    Safety Issue?: No

Inclusion Criteria:

For screening:

• Female, age 18 or over
• Present to a study midwife with suspected pregnancy
• Live in a study village

For the main study:

• Infected with S. japonicum
• Pregnancy as determined by urine pregnancy test
• Age 18 or older
• Participant is otherwise healthy as determined by history, physical exam, ultrasound and laboratory assessment
• Pregnancy between 12-16 weeks gestation
• Ability to provide informed consent to participate
• Infants born to these women will also be included in this study.

Exclusion Criteria:

• Presence of significant disease/illness that is either acute or chronic. This will be defined by history, physical examination, ultrasound and laboratory assessment. In particular:
• History of seizures or other neurologic disorder, chronic medical problem determined by history or physical examination, e.g. active hepatitis, tuberculosis, heart disease.
• Grade 3 or higher laboratory abnormality of BUN, Creatinine, bilirubin, white blood cell count, or platelet count will warrant exclusion. Grade 2 or higher abnormality of ALT or AST will warrant exclusion. For hemoglobin, women with severe anemia defined as hemoglobin less than 7.0 g/dl will be excluded.
• Women with myoma on ultrasound that are sub-mucosal or women with myoma that are in any location and greater than 5 cm in size.
• Women with congenital anomalies of the reproductive tract that would be expected to cause decreased fetal weight or greatly increase the risk of prematurity such as duplicate uterus, uterine septum.
• For less clear cases, the researchers will define significant illness as one that significantly alters a woman's ability to perform activities of daily living, causes symptoms at least two days per week, or necessitates regular use of medication. In the case of acute medical conditions such as urinary tract infection, pneumonia, febrile illness, enrollment may be postponed until the illness is successfully treated (not currently on any medication for the illness) or the illness itself resolves if this occurs before 16 weeks gestation.
• Presence of cysts in the eye suggestive of neurocysticercosis.
• Regular use of a medication for a chronic medical condition.
• History of severe allergic reaction (anaphylaxis, facial swelling, or difficulty breathing) or seizure with praziquantel administration.
• Fetus has congenital anomaly determined by 12-16 week ultrasound or is determined to be nonviable (e.g. blighted ovum).
• Twin or higher order pregnancy.
• Woman has been enrolled into this study for a previous pregnancy.
• Inability to comprehend study procedures and provide informed consent due to limited cognitive abilities or other, or refuses to provide informed consent.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Overall Contact: Jennifer Friedman (401) 863-2127 

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00486863

Study ID Number: 06-0039

ClinicalTrials.gov Identifier: NCT00486863

Health Authority: Philippines: Department of Health