Kalium phosphoricum comp. in patients with neurasthenia: a randomized, double-blind, placebo-controlled clinical trial

Abstract

Objective

This Phase IV placebo-controlled clinical trial was designed to demonstrate the efficacy and safety of the product Neurodoron (Kalium phosporicum comp., KPC) in patients with neurasthenia.

Methods

This monocenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (registration number: DRKS00003261) was conducted in an outpatient German trial site. Women and men aged 18 and above were randomized to receive either KPC or placebo if they reported typical symptoms of neurasthenia and a severe psychiatric disorder could be excluded. The primary objectives were a reduction in characteristic symptoms of nervous exhaustion and perceived stress as well as improvement in general health status after 6 weeks of treatment.

Results

In total, 204 patients underwent screening, 78 were randomized in each treatment group, and 77 patients each received treatment (intention-to-treat (ITT) population = 154 patients). For none of the primary efficacy variables, an advantage in favor of KPC could be demonstrated in the pre-specified analysis (p-values between 0.505–0.773, Student’s t-test). In a post-hoc analysis of intra-individual differences after 6 weeks treatment, a significant advantage of KPC vs. placebo was shown for characteristic symptoms of nervous exhaustion (irritability (p = 0.020); nervousness (p = 0.045), Student’s t-test). Adverse event (AE) rates were similar between treatment groups, in both groups six AEs were assessed as causally related to treatment (severity mild or moderate). No AE resulted in discontinuation of treatment.

Conclusions

Trial treatment was well tolerated with only a few and minor AEs reported, confirming the markedly good safety of KPC. A significant improvement of neurasthenia was seen for the total study population at the end of the treatment period. Superiority of KPC vs. placebo could not be demonstrated with the pre-specified analysis with regards to a sum score of 12 typical symptoms, perceived stress, or general health status. However, the explorative post-hoc analysis revealed that KPC is superior to placebo in the characteristic symptoms irritability and nervousness. KPC could therefore be a beneficial treatment option for symptomatic relief of neurasthenia.

Keywords:

• Neurodoron
• anthroposophic medicine
• nervous exhaustion
• neurasthenia
• stress
• irritability
• randomized controlled trial

Transparency

Declaration of funding

The trial was financed by the Weleda AG, Arlesheim, Switzerland.

Declaration of financial/other relationships

RH and LS are employees of Weleda AG, Germany. JH is the CEO of daacro GmbH & Co. KG, a clinical research organization in Germany and declares having received an honorarium for writing the publication. No further interests have to be declared. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

RH was responsible for the conception, design, and conduct of the trial. LS and JH drafted the manuscript and contributed substantially to the interpretation of the data. All authors reviewed the manuscript rigorously and critically and approved the final article.

Acknowledgements

The authors would like to thank the clinical trial personnel of Emovis GmbH, a dedicated study site situated in Berlin, Germany, for the conduct of the RCT, the responsible persons of the CRO ACM Allied Clinical Management GmbH for their excellent trial management and monitoring, and the responsible persons from CSG Clinische Studien Gesellschaft (IGES Group) for their input regarding data management and statistics. The authors’ thanks also go to Cristina Semaca (former employee of Weleda AG) who took care of data analyses and their correctness, and Martin Schnelle for his contribution to the trial design and input for any medical matters. Also, we are grateful for the dedicated personnel of daacro GmbH & Co. KG for their support in writing the manuscript. Special thanks go to all the anonymous patients for their valuable contribution to the trial.

Data availability statement

The data that support the findings of this clinical trial are not publicly available due to containing information that could compromise the privacy of research participants. Disclosure of data would not be in accordance with the European General Data Protection Regulation.

Ethics approval and consent to participate

This clinical trial has been registered on the “German Clinical Trials Register” (ID: DRKS00003261) and on EudraCT as 2010-024189-23. The trial protocol, informed consent document(s), and any other appropriate trial-related documents were reviewed and approved by an independent Ethics Committee (Ethik-Kommission des Landes Berlin, Ref. No. 11/0131 – ZS EK 14) and the relevant regulatory authorities (German Federal Institute for Drugs and Medical Devices (BfArM)). There were no trial protocol amendments. All trial patients gave their written informed consent to participate in the clinical trial prior to any trial related procedures.

Notes

i Neurodoron is a registered trademark of Weleda Trademark AG P-569108 Switzerland, National Trademark Registration, 006345516 European Union, Regional Trademark Registration.