A Pilot Feasibility Trial of Prenatal and Early Postnatal Fluoxetine Treatment for Intellectual Impairments of Down Syndrome

Study ID
STU 032014-006

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)
  • UT Southwestern Ambulatory Services
  • UT Southwestern-Other
  • Zale Lipshy University Hospital

Contact
Teresa O'Leary
214/648-4605
Teresa.OLeary@UTSouthwestern.edu

Principal Investigator
Carol Tamminga, M.D.

Summary

The proposed study will be a randomized double-blind, placebo control design of a prenatal (2nd trimester) and early postnatal (until age 2 years) pharmacologic intervention of fluoxetine aimed at improving the developmental abilities of children with Down syndrome. We will also evaluate and monitor the level of adverse events/side effects/safety outcomes over the course of treatment for those taking fluoxetine vs. placebo.

Study Drug Treatment:
Twenty-one participating mothers who meet the inclusion criteria, including gestation of 13-24 weeks, will be randomized in a 2:1 (fluoxetine:placebo) ratio as soon as baseline procedures are completed. Fluoxetine (or matching placebo) will be taken orally by the mother and initiated prenatally at 20 mg/d and increased weekly as tolerated to 80 mg/d and continued throughout pregnancy. after delivery, mothers will stop study drug.

Fluoxetine dosing in the neonate/infants/toddlers will be guided by clinical tolerability of study drug as assessed by Dr. Mary Carlin, the Director of the Down Syndrome Clinic at CMC anD by therapeutic drug monitoring (i.e., dosing guided by measured fluoxetine blood levels). Therapeutic drug monitoring will be conducted collectively by two expert pediatric pharmacologists in combination with an expert psychopharmacologist/psychiatrist, who will be unblinded to drug assignment to improve clinical decision making about dosing. Medication during this period will be prepared by the Children's Medical Center's investigational Drug Services and provided to the child participant's prescribing physician during their time in the study.

Prenatal Period:
During pregnancy, mothers will come to the uT Southwestern Medical Center obstetrics Clinic monthly where vital signs and side effects of study drug will be checked and study drug will be dispensed. Dr. Robyn Horsager-Boehrer, a uTSW obstetrician with expertise in maternal-fetal medicine, will oversee these visits. We will request that mothers bring copies of records from their regular obstetrician so that Dr. Horsager-Boehrer can review these for any concerns; however, these will noT be regular obstetrical care visits. Mothers will continue to receive routine prenatal care from their regular obstetrician.

Postnatal Period:
after birth, clinical care of neonate/infant/toddler participants will be provided by Mary Carlin, M.D., Clinical associate Professor of Pediatrics at uTSW and Director of the Children's Medical Center Down Syndrome Clinic. Dr. Carlin will evaluate children twice during the neonatal period, 3 and 12 weeks after birth, and then every 3 months for 2 years and more frequently as clinically indicated. The visits at 3 months, 12 months, and 2 years of age will be delivered by Dr. Carlin as part of standard care. The remaining visits are being done specifically for the research project (i.e., are not considered standard care).

The primary outcomes of the study will assess the feasibility and safety of the trial design and intervention in the proposed population. Feasibility will be assessed by: a) viability of subject recruitment and rate of enrollment; (b) adherence to study visits, scheduled assessments, and study medication, and; (c) dropout rates by treatment group. Safety will be assessed by spontaneously reported or observed adverse events as well a detailed side effects/adverse events form (the latter completed at each visit).

The principal efficacy outcome, assessed at 6 months and 1 and 2 years, will be a broad measure of neurodevelopment-the composite score of the Bayley Scales of infant Development-Third edition.

Participant Eligibility

1. Mothers with a fetus with a DS diagnosis confirmed by chorionic villus sampling or the new noninvasive prenatal testing (NIPT) of maternal blood.

2. Gestation between 13 and 24 weeks.

3. 18+ years of age.

4. Mothers and fathers (except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest) who demonstrate adequate decisional capacity to make a choice about participating in this research study and who provide informed consent to participate.