Bryophyllum Pinnatum Treatment of Anxiety Related to Signs of Preterm Birth

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Anxiety, Preterm Labor

Intervention / Treatment
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* Drug: Bryophyllum 50% chewable tablets
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 48 h after hospitalisation patients can be randomized to the Bryophyllum group or the placebo group.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bryophyllum 50%<br>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<br>* 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<br>|
| Placebo Comparator: Placebo<br>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<br>* Lactose with adaption in appearance and tast<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bryophyllum pinnatum, Anxiety, Preterm labor, Sleep quality, Phytotherapy