Preterm LaborPhase 2NCT05110599
Bryophyllum Pinnatum Treatment of Anxiety Related to Signs of Preterm Birth
A Phase 2 study testing Bryophyllum 50% chewable tablets in people with Preterm Labor and Anxiety, run by Christian Haslinger at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preterm Labor, Anxiety
- What is being tested?
- Bryophyllum 50% chewable tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteSwitzerland
- Study dates
- 12 Jul 2022to 1 Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Preterm Labor, Anxiety
- Being tested
- Bryophyllum 50% chewable tablets, Placebo
- Keywords
- Bryophyllum pinnatum, Anxiety, Preterm labor, Sleep quality, Phytotherapy
- Medical subject headings
- Obstetric Labor, Premature, Anxiety Disorders, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bryophyllum 50% chewable tabletsDrug
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
PlaceboOther
Lactose with adaption in appearance and tast
| Study group | Role | What they receive |
|---|---|---|
| Bryophyllum 50% | Active comparator | 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. Receives: Drug: Bryophyllum 50% chewable tablets |
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: assessment before treatment, after 1 week and after 2 weeks
Secondary outcomes (4)
change in sleep quality
assessed with Pittsburgh Sleep Quality Index (PSQI) values from 0 to 21, higher scores indicating worse sleep quality
Measured: assessment before treatment, after 1 week and after 2 weeks
hospitalisation days
Measured: from randomisation till birth or end of preterm period, whichever came first, up to 9 weeks.
reached gestational age
Measured: at birth
incidence of Adverse Events
occurence of Adverse Events
Measured: up to 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2021
- Study start12 Jul 2022
- Primary completion25 Aug 2023
- Study completion1 Oct 2023
Why it stopped: Slow recruitment and expired study medication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Preterm LaborStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 48 h after hospitalisation patients can be randomized to the Bryophyllum group or the placebo group.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christian Haslinger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Christian Haslinger, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05110599
- Sponsor's protocol ID
- BASEC-Nr. 2021-00941
- Status last verified
- Dec 2023
- First submitted
- 5 Oct 2021
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 27220081Plangger 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.
PubMed 16051414Simoes-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.
PubMed 23343584Lambrigger-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.
PubMed 24373544Simoes-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.
PubMed 29945146Santos 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.
PubMed 30562827Santos 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.
PubMed 31685022Santos 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.
PubMed 33679416
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bryophyllum Pinnatum Treatment of Anxiety Related to Signs of Preterm Birth: a Randomised, Double-blind, Placebo-controlled Study as Investigator-Initiated Trial
- ClinicalTrials.gov ID
- NCT05110599
- Acronym / sponsor ID
- BASEC-Nr. 2021-00941
- Conditions
- Preterm Labor, Anxiety
- Keywords
- Bryophyllum pinnatum, Anxiety, Preterm labor, Sleep quality, Phytotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment and expired study medication.
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Christian HaslingerUniversity, hospital or other
- Study start
- 12 Jul 2022 (actual)
- Primary completion
- 25 Aug 2023 (actual)
- Study completion
- 1 Oct 2023 (actual)
- First posted
- 8 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 48 h after hospitalisation patients can be randomized to the Bryophyllum group or the placebo group.
| Arm | Type | Receives |
|---|---|---|
| Bryophyllum 50% | Active comparator | Drug: Bryophyllum 50% chewable tabletsParticipants 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. |
| Placebo | Placebo comparator | Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bryophyllum 50% chewable tabletsEach 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 | Drug | Bryophyllum 50% |
| PlaceboLactose with adaption in appearance and tast | Other | Placebo |
Primary outcome
change in situational state of anxiety
Time frame: Assessment before treatment, after 1 week and after 2 weeks
assessed with State-Trait-Anxiety-Inventory (STAI) values from 20 to 80, higher scores indicating worse state of anxiety
change in situational state of anxiety
Time frame: assessment before treatment, after 1 week and after 2 weeks
assessed with Pregnancy-related Anxiety Questionnaire Revised 2 (PRAQ-R2) values from 10 to 50, higher scores indicating worse state of anxiety
4 secondary outcomes
change in sleep quality
Time frame: assessment before treatment, after 1 week and after 2 weeks
hospitalisation days
Time frame: from randomisation till birth or end of preterm period, whichever came first, up to 9 weeks.
reached gestational age
Time frame: at birth
incidence of Adverse Events
Time frame: up to 9 weeks
Results and safety
The study was stopped early (reason given: Slow recruitment and expired study medication.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Background: PubMed 27220081Furer 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.
- Background: PubMed 16051414Plangger 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.
- Background: PubMed 23343584Simoes-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.
- Background: PubMed 24373544Lambrigger-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.
- Background: PubMed 29945146Simoes-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.
- Background: PubMed 30562827Santos 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.
- Background: PubMed 31685022Santos 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.
- Background: PubMed 33679416Santos 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bryophyllum 50% chewable tablets in people with Preterm Labor and Anxiety, run by Christian Haslinger at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment and expired study medication.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in situational state of anxiety (time frame: Assessment before treatment, after 1 week and after 2 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05110599, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.