Clinical trial NCT06940323: Pregnancy Registry, Infants, Serum/Milk Analysis (PRISMA)
Official title: Pregnancy Registry, Infants, Serum/Milk Analysis (PRISMA): Pregnancy Registry for Women With Chronic Conditions
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Clinically Isolated Syndrome
NMOSD
Myasthenia Gravis
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2025-04-23
Enrollment: 250
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult women diagnosed with multiple sclerosis (MS), clinically isolated syndrome (CIS), Neuromyelitis optica spectrum disorder (NMOSD), and/or myasthenia gravis who are planning pregnancy, currently pregnant, or postpartum.

Brief summary: PRISMA, is a pregnancy registry study, focused on comprehensively collecting information about pregnancy in women with chronic neurological conditions from across the United States and internationally.

Depending on their specific condition (MS, CIS, NMOSD, or other) and their specific treatment, participants will be asked to contribute to different aspects of the study. (1) The biosamples will be blood, breast milk, infant stool, maternal stool and vaginal swab samples, collected at specific time points. (2) The online surveys will be collected at specific time points. All study activities will be discussed with participants upon enrollment.

By collecting this information, the investigators hope to gain deeper insights into the relationship between pregnancy, the neurological condition, and maternal and infant health. For example, one of the sub-studies focuses on breast milk collection for women planning postpartum treatment with Ocrevus, Rituxan, Briumvi or Kesimpta.

This study is fully remote and all sample collection is optional, so participants can choose which types of samples they wish to provide. For blood draws, participants can schedule a home visit through ExamOne, making participation even more convenient.

The investigators aim to enroll women with chronic neurological conditions who are planning pregnancy, currently pregnant, or within one year postpartum.

Detailed description: The aim of this project is to develop a repository of samples for women who are pregnant and have chronic conditions, including demyelinating diseases -- either multiple sclerosis (MS), clinically isolated syndrome (CIS) or NMOSD (neuromyelitis optica spectrum disorders), chronic inflammation --- inflammatory bowel disease (IBD), rheumatoid arthritis (RA), lupus, myasthenia gravis (MG), primary headache disorders, or other chronic neurological conditions. Please note that the investigators refer to "MS" in the rest of the application.

This repository will include:

1. Maternal Outcomes (disease-related outcomes, depression, social support, breastfeeding and pregnancy-related outcomes):

   * Obtained via interviews, surveys, and medical record review during pregnancy planning, pregnancy (Baseline and 36w gestation) and postpartum (1, 4, 8, 12M)
   * Maternal radiographic information will be collected from data available in the medical records. \[Radiographic information will be information captured from the medical record, not obtained during the study visits. No radiology exams will be conducted as part of this research study. If deemed necessary for the subject's routine clinical care, the investigators will record the results of an MRI within 12M postpartum.\]
2. Infant Outcomes (growth, development, immunization, infection, breastfeeding, etc.)

   * Obtained via medical record review (up to 12M)
   * Monitored via maternal completion of the Ages and Stages Questionnaires-Version 3 (ASQ3) to track infant development outcomes (communication, gross motor, fine motor, problem solving, and person-social) at 2, 4, 6, 8, 10, and 12M of age.
3. Biospecimen Collection, Storage \& Later Batch Analysis:

   * Maternal blood samples will be collected for up to the following time points: Baseline (including if planning pregnancy), 3M gestation, 6M gestation, 8M gestation, 1M postpartum, 3M postpartum, and 6M postpartum. Samples will be processed and stored as serum, plasma and peripheral blood mononuclear cells (PBMCs).
   * Serial breastmilk samples will be collected, for both before and after treatment if applicable, and up to 2-3 years postpartum. These samples will be used to determine the concentrations of medications in breastmilk relative to maternal serum.
   * Serial maternal and infant gut microbiome samples will be collected before and after treatment (anytime during the lactation period which can extend up to 2-3 years postpartum) to determine the effect of mAb treatment on gut microbial populations in mothers and infants. Mothers will be asked to complete food frequency questionnaires for themselves and their infants at the time of each sample collection.
   * Maternal vaginal swab sample will be collected in their 36 weeks of gestation (OR 8M pregnancy) to determine the effect of mAb treatment on vaginal microbial populations in mothers. Mothers will be asked to complete questionnaires regarding their diet and medication for themselves at the time of each sample collection.
   * Serial maternal blood samples will be collected (including before and post treatment) anytime up to 2-3 years postpartum. These samples will be used to determine concentrations of medications in breastmilk relative to serum and to determine the effect of maternal treatment on mother and infant gut microbiome.

     * Timing of sample collection for participants treated with mAb will depend on the treatment type, dosing and infusion schedule.

Participants who are healthy controls or who are not receiving specific medications of interest will provide

* A single breastmilk sample at 2M, 3M, and 4M
* A maternal and infant gut microbiome sample at 2M, 3M, and 4M postpartum
* Maternal vaginal swab sample at 36 weeks of gestation (OR 8M pregnancy).
* Maternal blood samples will be collected at corresponding timepoints 2M, 3M and 4M postpartum (to be processed and stored as serum, plasma, and PBMCs)

Eligibility criteria: Inclusion Criteria:

* Pregnant or contemplating pregnancy
* Female, aged 18 to 64 years
* Diagnosis of one of the following conditions:
* Clinically Isolated Syndrome (CIS) or Multiple Sclerosis (MS), based on the 2010 McDonald Criteria
* Neuromyelitis Optica Spectrum Disorder (NMOSD)
* Inflammatory Bowel Disease (IBD)
* Rheumatoid Arthritis (RA)
* Myasthenia Gravis
* Lupus
* Other chronic neurological conditions
* Willing to provide biosamples and/or complete surveys at specified timepoints
* Women without a chronic condition who are pregnant or contemplating pregnancy (as part of the control group)

Exclusion Criteria:

- Unwillingness to provide informed consent

Primary outcomes:
measure: Maternal Disease Activity During Pregnancy and Postpartum Assessed by Expanded Disability Status Scale (EDSS)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Disease Activity During Pregnancy and Postpartum Assessed by MRI Findings
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Disease Treatment Course During Pregnancy and Postpartum Assessed by Disease Modifying Therapy (DMT) Use
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Disease Activity During Pregnancy and Postpartum Assessed by Clinical Relapse Rates
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
Secondary outcomes:
measure: Infant Growth and Development Outcomes Assessed by Chart Review and ASQ-3
timeFrame: From birth through 12 months postpartum
measure: Detection and Concentration of Monoclonal Antibodies in Breastmilk
timeFrame: From first infusion postpartum through 12 months postpartum
measure: Concentration of Monoclonal Antibodies and Disease-Related Biomarkers in Maternal Blood
timeFrame: From the planning pregnancy (if applicable) to 6 months postpartum
measure: Maternal Fatigue During Pregnancy and Postpartum Assessed by Modified Fatigue Impact Scale (MFIS)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Sleep Quality During Pregnancy and Postpartum Assessed by Medical Outcomes Study Sleep Scale (MOS-SS)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Sleep Quality During Pregnancy and Postpartum Assessed by Epworth-Sleepiness Scale (ESS)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Cognitive Function During Pregnancy and Postpartum Assessed by Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Social Support During Pregnancy and Postpartum Assessed by Medical Outcomes Study Social Support Survey (19-Item Version)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Per-partum Depression Status During Pregnancy and Postpartum Assessed by Hospital Anxiety and Depression Scale (HADS)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Per-partum Depression Status During Pregnancy and Postpartum Assessed by Edinburgh Postnatal Depression Scale (EPDS)
timeFrame: From pre-pregnancy (if applicable) through 12 months postpartum
measure: Maternal Per-partum Depression Status During Pregnancy and Postpartum Assessed by Mini International Neuropsychiatric Interview (MINI)
timeFrame: 12 months postpartum
measure: Maternal Per-partum Depression Status During Pregnancy and Postpartum Assessed by Structured Clinical Interview for DSM-5 (SCID)
timeFrame: 12 months postpartum
measure: Maternal Bonding with Infant Assessed by Mother-to-Infant Bonding Scale (MIBS)
timeFrame: From 1 month through 12 months postpartum
measure: Infant Feeding Practices Assessed by Breastfeeding Questionnaire
timeFrame: From 1 month through 12 months postpartum
Other outcomes:
measure: Exploratory: Changes in Maternal Gut Microbiome Composition Following Maternal Monoclonal Antibody Treatment
timeFrame: Pre-infusion through 60 days post-infusion
measure: Exploratory: Changes in Infant Gut Microbiome Composition Following Maternal Monoclonal Antibody Treatment
timeFrame: Pre-infusion through 60 days post-infusion
measure: Exploratory: Infant Medical Problems Inflicting Immune Functions
timeFrame: From delivery through 12 months postpartum
measure: Exploratory: Changes in Maternal Vaginal Microbiome Composition During Pregnancy
timeFrame: 36 weeks of gestation (OR 8M pregnancy)
Locations:
city: San Francisco
country: United States
facility: University of California-San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Riley Bove, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Anderson A, Krysko KM, Rutatangwa A, Krishnakumar T, Chen C, Rowles W, Zhao C, Houtchens MK, Bove R. Clinical and Radiologic Disease Activity in Pregnancy and Postpartum in MS. Neurol Neuroimmunol Neuroinflamm. 2021 Feb 19;8(2):e959. doi: 10.1212/NXI.0000000000000959. Print 2021 Mar.
citation: LaHue SC, Anderson A, Krysko KM, Rutatangwa A, Dorsey MJ, Hale T, Mahadevan U, Rogers EE, Rosenstein MG, Bove R. Transfer of monoclonal antibodies into breastmilk in neurologic and non-neurologic diseases. Neurol Neuroimmunol Neuroinflamm. 2020 May 27;7(4):e769. doi: 10.1212/NXI.0000000000000769. Print 2020 Jul.
citation: Anderson A, Rowles W, Poole S, Balan A, Bevan C, Brandstadter R, Ciplea AI, Cooper J, Fabian M, Hale TW, Jacobs D, Kakara M, Krysko KM, Longbrake EE, Marcus J, Repovic P, Riley CS, Romeo AR, Rutatangwa A, West T, Hellwig K, LaHue SC, Bove R. Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions. Ann Clin Transl Neurol. 2023 Nov;10(11):2053-2064. doi: 10.1002/acn3.51893. Epub 2023 Sep 7.