Clinical trial NCT05110599: Bryophyllum Pinnatum Treatment of Anxiety Related to Signs of Preterm Birth
Official title: Bryophyllum Pinnatum Treatment of Anxiety Related to Signs of Preterm Birth: a Randomised, Double-blind, Placebo-controlled Study as Investigator-Initiated Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Preterm Labor
Anxiety
Keywords: Bryophyllum pinnatum
Anxiety
Preterm labor
Sleep quality
Phytotherapy
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2021-11-08
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 48 h after hospitalisation patients can be randomized to the Bryophyllum group or the placebo group.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: change in situational state of anxiety
timeFrame: Assessment before treatment, after 1 week and after 2 weeks
measure: change in situational state of anxiety
timeFrame: assessment before treatment, after 1 week and after 2 weeks
Secondary outcomes:
measure: change in sleep quality
timeFrame: assessment before treatment, after 1 week and after 2 weeks
measure: hospitalisation days
timeFrame: from randomisation till birth or end of preterm period, whichever came first, up to 9 weeks.
measure: reached gestational age
timeFrame: at birth
measure: incidence of Adverse Events
timeFrame: up to 9 weeks
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: University Hospital Zurich
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.