Endeavor to Stop Nausea/Vomiting Associated With Pregnancy (E-SNAP)

Pregnancy Clinical Trial

— ESNAP  

Official title:

Endeavor to Stop Nausea/Vomiting Associated With Pregnancy (E-SNAP)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05452174
• Other study ID #: STU00215676
• Secondary ID: R21HD105101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 13, 2022
• Est. completion date: October 29, 2023

Study information

• Verified date: April 2024
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: October 29, 2023
• Est. primary completion date: October 29, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperemesis Gravidarum
• Nausea
• Pregnancy
• Vomiting

Intervention

Drug:
• Mirtazapine
Mirtazapine, sold under the brand name Remeron, is an atypical antidepressant, and as such is used primarily to treat depression.

Locations

Country	Name	City	State
United States	Northwestern University Asher Center for the Study and Treatment of Depressive Disorders	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in Pregnancy Unique Quality of Emesis (PUQE) score	We will utilize the PUQE scale to capture the severity of nausea and vomiting in pregnancy based on three physical symptoms: nausea, vomiting, and retching over the previous 24 hours. A PUQE score of < 6 is considered mild, a score from 7-12 is moderate, and a score of 13+ is considered severe. This scale will be entered daily in REDCap directly by the participant.	daily for three weeks
Secondary	Self-Administered Comorbidity Questionnaire (SCQ)	The Comorbidity Questionnaire (CQ) assesses comorbid conditions in clinical and health services research. The questionnaire is self-administered, short, easily understood, and can be completed by individuals without any medical background. It also allows the subject to note the severity of each comorbid conditions and their perception of its impact on their function.	weekly for three weeks
Secondary	9-Item Patient Health Questionnaire (PHQ-9)	The 9-Item Patient Health Questionnaire (PHQ-9) is a self-administered instrument based on the nine DSM-5 criteria listed under criterion A for Major Depressive Disorder. The questionnaire includes criteria based diagnosis of depressive symptoms, assists in identifying treatment goals, determining severity of symptoms, as well as guiding clinical intervention. When considering a diagnosis, the clinician will use clinical interviewing skills to determine whether the symptoms are causing clinically significant distress or impairment and those symptoms are not better explained or attributed to other conditions, such as substance use, medical conditions, or bereavement.	weekly for three weeks
Secondary	Generalized Anxiety Disorder Scale, 7-item (GAD-7)	The Generalized Anxiety Scale is a 7-item self-report for symptoms consistent with the Diagnostic and Statistical Manual of Mental Disorders of generalized anxiety disorder.	weekly for three weeks
Secondary	Peripartum Events Scale (PES)	The Peripartum Events Scale (PES) captures data from several categories in the birth record. The following categories of events are included: medical and obstetric risk factors, time in operating room, fetal monitoring, surgical complications, infant anthropometrics and outcome, NICU admission, and postpartum complications (such as infection, hemorrhage). Admission to the special care nursery will also be noted. We have modified the original measure to align with current obstetrical practices. The PES will be completed for all enrolled participants.	weekly for three weeks
Secondary	PROMIS Global Health	The PROMIS Global Health item scale assesses overall health. The global health items include ratings of the five primary PROMIS domains (physical function, fatigue, pain, emotional distress, social health) as well as perceptions of general health that cut across domains.	weekly for three weeks
Secondary	Columbia-Suicide Severity Rating Scale (C-SSRS)	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment that was developed with NIMH support. The scale is evidence-supported and is part of a national and international public health initiative involving the assessment of suicidality. Suicidal ideation will be assessed at baseline, during, and 28 days after treatment cessation if there were any abnormalities during the trial.	weekly for three weeks
Secondary	plasma mirtazapine concentrations	Genotypes that determine the activities of CYP2D6, and minor pathways 3A4/5 and 1A2, will be explored for associations with mirtazapine plasma concentrations.	weekly for three weeks