Clinical trial NCT04825171: Perceived Changes in Anxiety Symptom Burden During Treatment With Bryophyllum Pinnatum and Tolerability
Official title: Perceived Changes in Anxiety Symptom Burden During Treatment With Bryophyllum Pinnatum and Tolerability: a Prospective, Single-Group Pre-post Observational Study as Investigator-Initiated Trial (IIT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anxiety Symptoms
Keywords: Anxiety
Depression
Stress
Sleep Quality
Internal Coherence
Lead sponsor: Klinik Arlesheim
Sponsor class: OTHER
First posted: 2021-04-01
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Bryophyllum pinnatum (BP) is a succulent perennial plant from the family Crassulacea (for reviews see Fürer 2016 and Hamburger 2017). Leaf extracts from BP have been used in traditional medicine to treat wounds and ulcers, skin diseases, infections, inflammations, pain, diabetes, hypertension, and cancer. In Europe, BP started to be used at the beginning of the 20th century in Anthroposophic medicine, a form of holistic medicine with an integrative approach. Almost a hundred years later, BP preparations are still often prescribed in Anthroposophic medicine, where it is used in the treatment of a broad spectrum of diagnoses, most often of mental and behavioural disorders (ICD-10 F00-F99), including anxiety, depressive, and sleep disorders (Simões-Wüst 2012).

In Switzerland, during the last decade, BP (50 % tablets) started to be used in conventional settings mainly in the treatment of preterm labour (Simões-Wüst 2018, Plangger 2006), overactive bladder (Betschart 2013), sleep disorders (Simões-Wüst 2015), and restless legs syndrome (Von Manitius 2019).

Whereas the good effectiveness of BP preparations in the treatment of preterm contractions and overactive bladder is well supported by data obtained using a variety of in vitro models (see e.g. Santos 2018, Bachmann 2017, Simões-Wüst 2010), less is known about possible mechanisms of action that would support their use in the treatment of mental and behavioural disorders.

Nevertheless, the observed improvements of sleep disorders are corroborated by animal experiments showing that different fractions of the leaf extract of BP can prolong the pentobarbitone-induced sleeping time (Yemitan 2005 and Pal 1999), indicating a CNS depressant action. Some of the bufadienolides present in Bryophyllum species are thought to be responsible for the sedative effects (Wagner 1986).

The aim of the present study is to find out if patients suffering from anxiety symptoms perceive improvements of these symptoms during treatment with Bryophyllum 50% tablets. Since anxiety symptoms are often related to depression, reduced sleep quality, stress, reduced health-related quality of life and the feeling of not being able to control owns life (internal coherence), these aspects will be assessed as well.

Detailed description: The present IIT (Investigator-Initiated Trial) study is a prospective, single-group, pre-post study (phase IV).

A past study showed that among Anthroposophical physicians the most frequent diagnosis group where BP preparations are prescribed are mental and behavioural disorders such as anxiety and sleep disorders. In the present study, we, therefore, want to investigate the effectiveness of Bryophyllum tablets in patients with anxiety symptoms.

Study participants will be recruited among the patients on the waiting list of the Department of Psychiatry and Psychosomatics at the Clinic Arlesheim.

* Participant recruitment will continue until 60 patients have concluded the study.
* Recruitment period will probably last 15 months.
* Duration of the drug administration is 3 weeks.

Participants will fill in a questionnaire three times. At baseline, after two and after three weeks of Bryophyllum intake.

Eligibility criteria: Inclusion Criteria:

* Patients referred by their treating physician to the Department of Psychiatry and Psychosomatic of the Clinic Arlesheim waiting for the in-stay
* Expected waiting time until in-stay is at least two weeks
* Patients having anxiety symptoms as measured by the GAD-2 questionnaire (cut-off of 3 points)
* Patients'state of health allows them to complete the questionnaire on their own
* Signed informed consent
* No treatment with BP during the last two months
* No planned doses increase of (conventional) anxiolytics or antidepressants for the duration of the period until in-stay
* Age over 18 years
* Good German knowledge (at least level B2 from Common European Framework of Reference for Languages)

Exclusion Criteria:

* Wheat allergies
* Acute life-threatening conditions
* Withdrawal of informed consent

Primary outcomes:
measure: Change of anxiety symptoms
timeFrame: 2 weeks
Secondary outcomes:
measure: Change of anxiety symptoms
timeFrame: 3 weeks
measure: Change of anxiety symptoms
timeFrame: 2 and 3 weeks
measure: Change of depression symptoms
timeFrame: 2 and 3 weeks
measure: Change of stress symptoms
timeFrame: 2 and 3 weeks
measure: Change in sleep quality
timeFrame: 2 and 3 weeks
measure: Change in health-related quality of life questionnaire
timeFrame: 2 and 3 weeks
measure: Change in the Sense of Coherence
timeFrame: 2 and 3 weeks
measure: Brophyllum Prescription report
timeFrame: 3 weeks
Other outcomes:
measure: Incidence of any Adverse Events (Safety)
timeFrame: 2 and 3 weeks
Locations:
city: Arlesheim
country: Switzerland
facility: Klinik Arlesheim
state: Basel Land
Study officials:
affiliation: Klinik Arlesheim, Pfeffingerweg1, 4144 Arlesheim, Switzerland
name: Markus Schlemmer, Dr. med.
role: PRINCIPAL_INVESTIGATOR
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: M. Hamburger, O. Potterat, K. Fürer, A. P. Simões-Wüst, and U. Von Mandach, "Bryophyllum pinnatum - Reverse engineering of an anthroposophic herbal medicine," in Natural Product Communications, 2017, vol. 12, no. 8, pp. 1359-1364.
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: Betschart C, von Mandach U, Seifert B, Scheiner D, Perucchini D, Fink D, Geissbuhler V. Randomized, double-blind placebo-controlled trial with Bryophyllum pinnatum versus placebo for the treatment of overactive bladder in postmenopausal women. Phytomedicine. 2013 Feb 15;20(3-4):351-8. doi: 10.1016/j.phymed.2012.10.007. Epub 2012 Dec 4.
citation: Schenkel L, Simoes-Wust AP, Hosli I, von Mandach U. Drugs in Pregnancy and Lactation - Medications Used in Swiss Obstetrics. Z Geburtshilfe Neonatol. 2018 Feb 8. doi: 10.1055/s-0043-124975. Online ahead of print.
citation: Furer K, Simoes-Wust AP, Winkler A, Amsler N, Schnelle M, von Mandach U. [The Application of Bryophyllum pinnatum Preparations in Obstetrics and Gynaecology - a Multicenter, Prospective Observational Study]. Forsch Komplementmed. 2015;22(4):231-6. doi: 10.1159/000437154. Epub 2015 Aug 3. German.
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: Pal S, Sen T, Chaudhuri AK. Neuropsychopharmacological profile of the methanolic fraction of Bryophyllum pinnatum leaf extract. J Pharm Pharmacol. 1999 Mar;51(3):313-8. doi: 10.1211/0022357991772312.
citation: Yemitan OK, Salahdeen HM. Neurosedative and muscle relaxant activities of aqueous extract of Bryophyllum pinnatum. Fitoterapia. 2005 Mar;76(2):187-93. doi: 10.1016/j.fitote.2004.11.009.
citation: H. Wagner, H. Lotter, and M. Fischer, "Die toxischen und sedierend wirkenden Bufadienolide von Kalanchoedaigremontiana HAMETet PERR," Helv. Chim. Acta, vol. 69, no. 2, pp. 359-367, 1986.
citation: Furer K, Raith M, Brenneisen R, Mennet M, Simoes-Wust AP, von Mandach U, Hamburger M, Potterat O. Two new flavonol glycosides and a metabolite profile of Bryophyllum pinnatum, a phytotherapeutic used in obstetrics and gynaecology. Planta Med. 2013 Nov;79(16):1565-71. doi: 10.1055/s-0033-1350808. Epub 2013 Sep 26.
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, Hassani TA, Muller-Hubenthal B, Pittl S, Kuck A, Meden H, Eberhard J, Decker M, Furer K, von Mandach U; Bryophyllum Collaborative Group. Sleep Quality Improves During Treatment With Bryophyllum pinnatum: An Observational Study on Cancer Patients. Integr Cancer Ther. 2015 Sep;14(5):452-9. doi: 10.1177/1534735415580680. Epub 2015 Apr 14.
citation: von Manitius S, Flugel D, Gievers Steinlein B, Schnelle M, von Mandach U, Simoes-Wust AP. Bryophyllum pinnatum in the treatment of restless legs syndrome: A case series documented with polysomnography. Clin Case Rep. 2019 Apr 14;7(5):1012-1020. doi: 10.1002/ccr3.2144. eCollection 2019 May.
citation: K. Beckler, "State-Trait Anxiety Inventory for Adults - Manual, Instrument and Scoring Guide," 1983 Consult. Psychol. Press. Inc. Mind Gard. Inc., pp. 0-78, 2010.
citation: N. Williams, "The GAD-7 questionnaire," Occup. Med. (Chic. Ill)., vol. 64, no. 3, p. 224, 2014.
citation: R. L. Spitzer, K. Kroenke, and J. B. W. Williams, "Validation and utility of a self-report version of PRIME-MD," Prim. Care Companion J. Clin. Psychiatry, vol. 2, no. 1, p. 31, 1999.
citation: Klein EM, Brahler E, Dreier M, Reinecke L, Muller KW, Schmutzer G, Wolfling K, Beutel ME. The German version of the Perceived Stress Scale - psychometric characteristics in a representative German community sample. BMC Psychiatry. 2016 May 23;16:159. doi: 10.1186/s12888-016-0875-9.
citation: M. Morfeld, I. Kirchberger, and M. Bullinger, SF-36 Fragebogen zum Gesundheitszustand: Deutsche Version des Short Form-36 Health Survey. Hogrefe, 2011.
citation: Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.