Clinical trial NCT05452174: Endeavor to Stop Nausea/Vomiting Associated With Pregnancy (E-SNAP)
Official title: Endeavor to Stop Nausea/Vomiting Associated With Pregnancy (E-SNAP)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Pregnancy
Severe Nausea and Vomiting
Hyperemesis Gravidarum
Keywords: pregnancy
severe nausea
vomiting
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-07-11
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this proposal is to conduct an early Phase 2 clinical trial to determine the acceptability, dosing, tolerability and safety of mirtazapine for severe nausea and vomiting of pregnancy (sNVP) that is not adequately responsive to current standard treatments. This plan mirrors clinical practice since commonly prescribed antiemetic/ antinauseant drugs will be tested for efficacy before treating with mirtazapine.

Detailed description: Translational Research in Maternal and Pediatric Pharmacology and Therapeutics (PAR-20-299) supports research to "enhance the usage of existing drugs or drug repurposing for safer and more effective treatment for pregnant women" for "the early and conceptual stages of these projects. The primary objective of this proposal is to conduct an early Phase 2 clinical trial to determine the acceptability, dosing, tolerability and safety of mirtazapine for severe nausea and vomiting of pregnancy (sNVP) that is not adequately responsive to current standard treatments. This plan mirrors clinical practice since commonly prescribed antiemetic/ antinauseant drugs will be tested for efficacy before treating with mirtazapine.

Mirtazapine is a promising drug to repurpose for sNVP. It has potent anti-emetic properties and is available as an oral disintegrating formulation. It is used off-label to treat NV during cancer chemotherapy, prevent post-surgical nausea and vomiting and for gastroparesis. It is marketed as the serotonin-norepinephrine reuptake inhibitor antidepressant Remeron®. Mirtazapine has multiple receptor effects beyond those involved in reducing depressive symptoms. In cancer and chemotherapy patients, it produces rapid resolution of nausea and vomiting by blocking physiologic inputs that coordinate emesis. It is hypothesized that repurposing mirtazapine for obstetric use overcomes the challenges of traditional pathways to develop new agents because its pharmacokinetics, safety and dosing have been established for general populations of patients and exposure data are available because it is prescribed to pregnant persons with depression.

Eligibility criteria: Inclusion Criteria:

* singleton pregnancy
* inpatient or outpatient status
* English speaking
* obstetrician's evaluation and diagnosis of sNVP or HG
* tolerance of oral disintegrating tablet at bedtime
* PUQE score of 10-15; moderate/high or severe
* refractory sNVP
* blood pressure range 70-200 / 45-120
* normal ECG

Exclusion Criteria:

* allergic or adverse reaction to mirtazapine
* patient has bipolar disorder
* subjects with active depression, or history of or current active suicidal ideation or attempt
* subjects with renal or hepatic impairment
* substance about in last 6 months
* use of medicinal or recreational cannabis-derived products in the last 6 months
* taking MAOIs, strong CYP3A inducers or inhibitors, and SSRIs

Primary outcomes:
measure: change in Pregnancy Unique Quality of Emesis (PUQE) score
timeFrame: daily for three weeks
Secondary outcomes:
measure: Self-Administered Comorbidity Questionnaire (SCQ)
timeFrame: weekly for three weeks
measure: 9-Item Patient Health Questionnaire (PHQ-9)
timeFrame: weekly for three weeks
measure: Generalized Anxiety Disorder Scale, 7-item (GAD-7)
timeFrame: weekly for three weeks
measure: Peripartum Events Scale (PES)
timeFrame: weekly for three weeks
measure: PROMIS Global Health
timeFrame: weekly for three weeks
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: weekly for three weeks
measure: plasma mirtazapine concentrations
timeFrame: weekly for three weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Asher Center for the Study and Treatment of Depressive Disorders
state: Illinois
Study officials:
affiliation: Northwestern University (adjunct) now at Children's National Hospital
name: Katherine L Wisner, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abramowitz A, Miller ES, Wisner KL. Treatment options for hyperemesis gravidarum. Arch Womens Ment Health. 2017 Jun;20(3):363-372. doi: 10.1007/s00737-016-0707-4. Epub 2017 Jan 9.
citation: Fejzo MS, MacGibbon KW, Wisner KL. Pregnant, miserable, and starving in 21st century America. AJOG Glob Rep. 2022 Dec 5;3(1):100141. doi: 10.1016/j.xagr.2022.100141. eCollection 2023 Feb.