Diphenhydramine for Labor Dystocia

(ACCEL Trial)

Overseen By Samantha Antonioli, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Category II/III tracing, Allergy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: During labor

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single IV dose of diphenhydramine (an antihistamine) can prevent labor arrest (when labor stops or slows significantly) and reduce the need for a cesarean delivery in first-time mothers. Participants will receive either the usual care or the experimental diphenhydramine treatment. The trial seeks first-time mothers who are at least 34 weeks pregnant, in active labor with a single baby, and have had their water break. Those with an allergy to diphenhydramine or certain heart rate patterns in the baby may not qualify. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that diphenhydramine, known as Benadryl, is generally safe to use during pregnancy. Studies suggest that medications like Benadryl often carry little risk. However, not all research completely agrees.

Since this trial is in the later stages (Phase 2/3), evidence suggests it is safe for humans. Earlier phases assessed basic safety, so the treatment is now expected to be safe for most people. Some studies have mentioned rare risks like cleft palate, but these findings remain uncertain. Always consult a healthcare provider to understand the possible risks and benefits for your situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for labor dystocia?

Most treatments for labor dystocia, like oxytocin or epidurals, aim to enhance uterine contractions or manage pain. Unlike these standard approaches, diphenhydramine—commonly known as an antihistamine used for allergies—may offer a novel way to address labor difficulties. Researchers are intrigued by diphenhydramine's potential to relax uterine muscles, possibly facilitating labor progress without the intense interventions typically required. This unique mechanism could provide a simpler, less invasive option for managing labor dystocia, sparking excitement about its potential benefits in maternity care.

What evidence suggests that diphenhydramine might be an effective treatment for labor dystocia?

This trial examines diphenhydramine, also known as Benadryl, for its potential benefits in managing slow or stalled labor. Participants may receive diphenhydramine as part of the treatment arm. Although typically used for allergies, diphenhydramine can relax muscles, potentially easing contractions and preventing labor from stopping. Previous studies have shown it works well for muscle issues, such as involuntary muscle contractions, suggesting it could help labor progress more smoothly. While direct data on its use for slow labor is limited, its mechanism supports its potential in this situation. Ongoing research will further clarify its role in managing labor. ^{6 7 8 9 10}

Who Is on the Research Team?

Samantha Antonioli, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for first-time mothers undergoing labor who may be at risk of labor stopping and needing a cesarean delivery. Participants must meet certain health standards, but specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

Primiparous

Category I tracing at time of inclusion

Ruptured membranes

Exclusion Criteria

Category II or III tracing

I am allergic to IV Diphenhydramine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of intravenous (IV) medication for the prevention of labor arrest and cesarean delivery

During labor

Follow-up

Participants are monitored for safety and effectiveness after treatment, including postpartum complications and neonatal adverse events

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Diphenhydramine

Trial Overview The study is testing the effectiveness of an IV medication, Diphenhydramine, against usual care in preventing labor from stopping and reducing the need for cesarean deliveries in new mothers.

How Is the Trial Designed?

Group I: Treatment with Diphenhydramine Experimental Treatment 2 Interventions

Group II: Usual Care Active Control 1 Intervention

Diphenhydramine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Benadryl for:

• Allergic reactions
• Insomnia
• Motion sickness
• Coughs and colds

Approved in European Union as Diphenhydramine for:

• Allergic reactions
• Insomnia
• Motion sickness
• Coughs and colds

Approved in Canada as Unisom for:

• Insomnia
• Allergic reactions

Approved in Japan as Sominex for:

• Insomnia
• Allergic reactions

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study of 111 mildly to moderately insomniac patients, diphenhydramine (50 mg) significantly improved sleep parameters, such as reducing the time it took to fall asleep, compared to a placebo.

Despite experiencing more side effects, patients preferred diphenhydramine over placebo and reported feeling more rested the next morning, supporting its use as an effective over-the-counter sleep aid for temporary insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diphenhydramine in insomniac family practice patients: a double-blind study. Rickels, K., Morris, RJ., Newman, H., et al.[2019]

A study using PET imaging confirmed that diphenhydramine, a common over-the-counter sleep aid, has a significant next-day residual sedative effect, with 44.7% H₁ receptor occupancy in the brain compared to only 16.6% for the second-generation antihistamine bepotastine.

Despite the measurable sedative effects of diphenhydramine, subjective feelings of sleepiness did not differ significantly among participants, highlighting the importance of caution when using OTC antihistamines for sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography. Zhang, D., Tashiro, M., Shibuya, K., et al.[2021]

In a study of 50 children with sleep disorders, diphenhydramine elixir (1.0 mg/kg) significantly reduced the time it took for children to fall asleep and the number of times they woke up during the night compared to a placebo.

Parents reported that diphenhydramine was more effective than placebo in improving overall sleep quality, indicating it is a safe and effective sleep aid for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of diphenhydramine HCI in pediatric sleep disorders. Russo, RM., Gururaj, VJ., Allen, JE.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36215142/

Midwifery Management of a Birthing Person with Cervical ... This case will discuss the use of intravenous diphenhydramine (Benadryl), the application of ice to the cervix, side-lying release, epidural analgesia use.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/7710376/

Diphenhydramine is effective in the treatment of idiopathic ... Diphenhydramine therapy was associated with minimal side effects, and it was most effective in treating patients with dystonia who experienced lightning jerks.

3. ninercommons.charlotte.edu ninercommons.charlotte.edu/record/2737/files/Lisenbee_uncc_0694D_13889.pdf

when childbirth progress slows or stalls: a qualitative This data about outcomes following healthcare professionals' predictions emerged unexpectedly ... adverse outcomes following labor dystocia. (e.g., hemorrhage/ ...

4. institutionalrepository.aah.org institutionalrepository.aah.org/cgi/viewcontent.cgi?article=2010&context=jpcrr

Calcium Carbonate as a Potential Intervention to Prevent ... Our focus was solely on calcium carbonate and its ability to prevent labor dystocia by increasing the effectiveness of uterine contractions.

5. hyperemesis.org hyperemesis.org/HER-Research/downloads/PDF%20Antihistamine%20Adverse%20Outcome%20EURO8079.pdf

This article appeared in a journal published by Elsevier. ... published outcome data come to the same conclusion that HG is significantly associated with low birth weight, small for gestational age, and preterm birth ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4474179/

Antihistamines and Birth Defects: A Systematic Review of ... Based on data from over 25,000 pregnancies in Sydney, Australia from 1956-1961, McBride reported a prevalence of cleft palate of 4.4 per 1,000 among 1,125 women ...

7. birthinjurycenter.org birthinjurycenter.org/what-to-avoid-while-pregnant/medications/

Medications to Avoid While Pregnant Which medications are safe to take while pregnant? · Benadryl · Claritin · Zyrtec · Sudafed (after the first trimester) · Mucinex · Robitussin.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1096719224000374

Outcomes in 14 live births resulting from Pegvaliase- ... Nine of 14 pregnancies were delivered by cesarian-section due to multiple pregnancy (one set of triplets), preeclampsia/HPTN (3), breech presentation (1), ...

9. drugsandalcohol.ie drugsandalcohol.ie/34343/1/Maternal_fetal_and_child_outcomes_of_mental_health_treatments_in-women.pdf

Maternal, Fetal, and Child Outcomes of Mental Health ... Suggested language for acknowledgment: This work was based on an evidence report, Maternal, Fetal, and Child. Outcomes of Mental Health Treatments in Women: A ...

10. stacks.cdc.gov stacks.cdc.gov/view/cdc/118090/cdc_118090_DS1.pdf

Use of antihistamine medications during early pregnancy ... Although antihistamines are generally considered safe during pregnancy, results from published studies are inconsistent. Methods: Using a case– ...