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.

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.

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.

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.

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

assessed with State-Trait-Anxiety-Inventory (STAI) values from 20 to 80, higher scores indicating worse 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

assessed with Pittsburgh Sleep Quality Index (PSQI) values from 0 to 21, higher scores indicating worse sleep quality

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

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