Bryophyllum Pinnatum Treatment of Anxiety Related to Signs of Preterm Birth

Bryophyllum Pinnatum Treatment of Anxiety Related to Signs of Preterm Birth: a Randomised, Double-blind, Placebo-controlled Study as Investigator-Initiated Trial

The present IIT (Investigator-Initiated Trial) study is a prospective, randomised, placebo-controlled, double blind trial.

Women hospitalised with signs of preterm birth can be recruited for the study. Participants will take study medication for 2 weeks (or until birth) and fill out a questionnaire at 3 time points (at baseline, after 1 week and after 2 weeks) to assess state of anxiety and sleep quality. Furthermore, information regarding adverse events and the further course of the pregnancy are recorded.

Study Overview

• Status: Terminated
• Conditions: Anxiety; Preterm Labor
• Intervention / Treatment: Drug: Bryophyllum 50% chewable tablets; Other: Placebo

Detailed Description

Preterm birth is one of the leading causes for mortality and morbidity in newborns and preterm contractions are the cause of a considerable part of preterm deliveries. In the treatment of preterm labour, tocolytic medications are often used that are associated with numerous side effects for the pregnant woman, which limits their use in time. Preparations from Bryophyllum pinnatum, which demonstrated excellent tolerability, constitute a safe alternative for tocolytic treatment. It was introduced as an alternative tocolytic by anthroposophic medicine in Europe and is used as a monotherapy or add-on therapy for preterm labour in many perinatal clinics in Switzerland today. In vitro studies support the use of B. pinnatum as a tocolytic.

In addition, there are also limited options for the treatment of mental disorders and sleep disturbances during pregnancy. Anxiety plays a major role in the development of preterm labour and often leads to administration of tocolytics longer than necessary. Preparations from B. pinnatum have traditionally been in the treatment of anxiety. Improvements of sleep quality in pregnant women during treatment with B. pinnatum preparations were already shown in previous studies.

This exploratory study aims at investigating the effects of B. pinnatum for the treatment of anxiety in patients with signs of preterm birth.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least 18 years old
• Hospitalisation with signs of preterm birth
• Gestational age at randomisation >22 weeks (22+0) and <35 weeks (34+6)
• Good German or English skills
• Written informed consent

Exclusion Criteria:

• Early premature rupture of the membranes (PPROM)
• Factors that make soon delivery likely (pre-eclampsia, suspect cardiotocography, clinical signs of an amniotic infection)
• Body temperature >38°C
• Cervical opening or cervical length < 5 mm
• Contraindication for B. pinnatum, lactose or wheat protein allergy
• Taking Bryophyllum 50% chewable tablets or powder 48 h before study inclusion
• Taking psychotropic drugs (Benzodiazepines, antidepressants, neuroleptics)
• Diagnosed psychiatric disease (depression, anxiety disorder, adaptation disorder, post- traumatic stress disorder, bipolar disorder)
• Active participation in another interventional study during the last 4 weeks
• Known or suspected non-compliance with study protocol
• Drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bryophyllum 50%; Participants of the verum group take Bryophyllum 50% chewable tablets starting the day after study inclusion. Participants take 2 tablets, four times a day for 2 weeks. If the birth takes place before the end of the 2 weeks, the study participation is terminated early.	Drug: Bryophyllum 50% chewable tablets; Each 350 mg tablet corresponds to 170 mg of leave press juice from Bryophyllum pinnatum, dried down to 17 mg by mixing with lactose; 100 mg dried BP matter in 1 g
Placebo Comparator: Placebo; Participants of the control group take Placebo chewable tablets starting the day after study inclusion. Participants take 2 tablets, four times a day for 2 weeks. If the birth takes place before the end of the 2 weeks, the study participation is terminated early.	Other: Placebo; Lactose with adaption in appearance and tast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in situational state of anxiety	assessed with State-Trait-Anxiety-Inventory (STAI) values from 20 to 80, higher scores indicating worse state of anxiety	Assessment before treatment, after 1 week and after 2 weeks
change in situational state of anxiety	assessed with Pregnancy-related Anxiety Questionnaire Revised 2 (PRAQ-R2) values from 10 to 50, higher scores indicating worse state of anxiety	assessment before treatment, after 1 week and after 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in sleep quality	assessed with Pittsburgh Sleep Quality Index (PSQI) values from 0 to 21, higher scores indicating worse sleep quality	assessment before treatment, after 1 week and after 2 weeks
hospitalisation days		from randomisation till birth or end of preterm period, whichever came first, up to 9 weeks.
reached gestational age		at birth
incidence of Adverse Events	occurence of Adverse Events	up to 9 weeks

Collaborators and Investigators

• Sponsor: Christian Haslinger

Publications and helpful links

General Publications

• Furer K, Simoes-Wust AP, von Mandach U, Hamburger M, Potterat O. Bryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy. Planta Med. 2016 Jul;82(11-12):930-41. doi: 10.1055/s-0042-106727. Epub 2016 May 24.
• Simoes-Wust AP, Lapaire O, Hosli I, Wachter R, Furer K, Schnelle M, Mennet-von Eiff M, Seifert B, von Mandach U. Two Randomised Clinical Trials on the Use of Bryophyllum pinnatum in Preterm Labour: Results after Early Discontinuation. Complement Med Res. 2018;25(4):269-273. doi: 10.1159/000487431. Epub 2018 Jun 22. No abstract available.
• Santos S, Haslinger C, Klaic K, Faleschini MT, Mennet M, Potterat O, von Mandach U, Hamburger M, Simoes-Wust AP. A Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In Vitro. Planta Med. 2019 Mar;85(5):385-393. doi: 10.1055/a-0810-7704. Epub 2018 Dec 18.
• Plangger N, Rist L, Zimmermann R, von Mandach U. Intravenous tocolysis with Bryophyllum pinnatum is better tolerated than beta-agonist application. Eur J Obstet Gynecol Reprod Biol. 2006 Feb 1;124(2):168-72. doi: 10.1016/j.ejogrb.2005.05.013. Epub 2005 Jul 26.
• Simoes-Wust AP, Jeschke E, Mennet M, Schnelle M, Matthes H, von Mandach U. Prescribing pattern of Bryophyllum preparations among a network of anthroposophic physicians. Forsch Komplementmed. 2012;19(6):293-301. doi: 10.1159/000345841. Epub 2012 Dec 17.
• Lambrigger-Steiner C, Simoes-Wust AP, Kuck A, Furer K, Hamburger M, von Mandach U. Sleep quality in pregnancy during treatment with Bryophyllum pinnatum: an observational study. Phytomedicine. 2014 Apr 15;21(5):753-7. doi: 10.1016/j.phymed.2013.11.003. Epub 2013 Dec 25.
• Santos S, Haslinger C, Mennet M, von Mandach U, Hamburger M, Simoes-Wust AP. Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study. BMC Complement Altern Med. 2019 Nov 4;19(1):292. doi: 10.1186/s12906-019-2711-5.
• Santos S, Zurfluh L, Mennet M, Potterat O, von Mandach U, Hamburger M, Simoes-Wust AP. Bryophyllum pinnatum Compounds Inhibit Oxytocin-Induced Signaling Pathways in Human Myometrial Cells. Front Pharmacol. 2021 Feb 18;12:632986. doi: 10.3389/fphar.2021.632986. eCollection 2021. Erratum In: Front Pharmacol. 2023 Feb 08;14:1141346.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Actual): August 25, 2023
• Study Completion (Actual): October 1, 2023

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: November 4, 2021
• First Posted (Actual): November 8, 2021

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Anxiety; Sleep quality; Preterm labor; Phytotherapy; Bryophyllum pinnatum
• Additional Relevant MeSH Terms: Mental Disorders; Pregnancy Complications; Obstetric Labor Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Anxiety Disorders; Premature Birth; Obstetric Labor, Premature
• Other Study ID Numbers: BASEC-Nr. 2021-00941

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No