Objective To investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-to-treatment pilot study with an oral SFE in patients with RRMS (NCT01450124). After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months. The primary outcome measures were the number and volume of contrast-enhancing lesions (CEL) measured in MRI during the 4-month treatment period compared with the 4-month baseline period. Eighty patients were screened at two centres, 38 patients were included in the trial, 28 completed the 8-month treatment period and 18 of these participated in the extension period.
Results The SFE significantly reduced the median number of monthly CELs from 1.00 (IQR 0.75–3.38) to 0.50 (IQR 0.00–1.13; difference −0.625, 95% CI −1.25 to −0.50; P<0.0001) at months 5–8. We observed significantly less brain atrophy as assessed by parenchymal brain volume change (P=0.0081). Adverse events were generally mild (57.7%) or moderate (38.6%) and comprised mainly gastrointestinal symptoms and minor infections. Mechanistic studies showed a significant increase in regulatory CD4+ T cell markers and a significant decrease in interleukin-17A-producing CD8+ T cells indicating a distinct mechanism of action of the study drug.
Interpretation The oral SFE was safe, tolerated well and exhibited beneficial effects on RRMS disease activity warranting further investigation in a controlled phase IIb or III trial.
Clinical trial registration NCT01450124; Results.
Statistics from Altmetric.com
Data Safety Monitoring Board Alessandra Solari (S.O.S.D. Neuroepidemiologia, Fondazione IRCCS Istituto Neurologico “C. Besta”, Milano, Italy), Ingo Kleiter (Neurologische Klinik, Ruhr Universität Bochum, Germany), Brigitte Wildemann (Neurologische Klinik, Universität Heidelberg, Heidelberg, Germany).
Contributors KHS, CH and RM designed the study. KHS, JPS, CH, JD, FP, S Schammler, SR, SF, LAIV, FH and OP collected the data. KHS, JPS, CH, JD, FP, SFl, S Siemonsen, GW, TF, OW, LAIV, FH and OP analysed the data. KHS and TF performed the statistical analysis. KHS, CH, OP and RM wrote the report. KHS, JPS, JD, FP, SF, S Schammler, SR, S Siemonsen, GW, TDF, TF, OW, LAIV and FH revised the report. All authors had full access to all of the data in the study. The corresponding author had the final responsibility for the decision to submit for publication.
Funding This work was supported by the Bundesministerium für Bildung und Forschung (BMBF, Förderkennzeichen 0315610-0315620 and Förderkennzeichen 16GW0082) in the context of NEU2. The INIMS at the Universitätsklinikum Hamburg-Eppendorf has been supported by the Hertie-Stiftung. The extension study was supported by Alpinia Laudanum, Switzerland. None of the funding sources had any role in designing the study, in collection, analysis, or interpretation of data, or in writing the article.
Competing interests KHS, JPS and CH report grants from the Bundesministerium für Bildung und Forschung, grants and provision of study drug from Alpinia Laudanum, during the conduct of the study. KHS reports grants from Biogen, outside the submitted work. JPS reports grants and personal fees from Biogen, personal fees from Genzyme, grants and personal fees from Novartis, grants from Merck Serono, outside the submitted work. JD reports grants, personal fees and non-financial support from Bayer Healthcare; grants, personal fees and non-financial support from Novartis, personal fees and non-financial support from Biogen, personal fees from Sanofi-Genzyme, personal fees from Allergan, personal fees from Merck Serono, outside the submitted work. FP reports grants and personal fees from various pharmaceutical companies, outside the submitted work. TF reports personal fees from Novartis, personal fees from Bayer, personal fees from Biogen, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Grünenthal, personal fees from Pharmalog, personal fees from SGS, personal fees from Roche, outside the submitted work. OP and LAIV report grants from Grant from the German Federal Ministry of Education and Research-BMBF (16GW0082), during the conduct of the study. CH has received funding for projects and invited talks from the following pharmaceutical companies: Biogen, Genzyme, Merck Serono, Roche. RM reports grants from the Ministry of Education and Research, grants from European Research Council, grants from Swiss National Science Foundation, grants from Swiss Commission for Technology and Innovation, grants from German Research Society, grants from Swiss MS Society, during the conduct of the study, grants and personal fees from Biogen, personal fees from Genzyme Sanofi Aventis, grants and personal fees from Novartis, personal fees from Roche, personal fees from Teva, personal fees from Merck AG, grants and personal fees from Cellprotect, personal fees from Neuway Pharma, outside the submitted work. GW, S Siemonsen, SR, SF, FH, TDF, OW and S Schammler declare no competing interest.
Ethics approval German Federal Institute for Drugs and Medical Devices (BfArM, Approval No. 4036771) and the local ethics committees (Approval No. PVN3389 and ZS EK 13572/09).
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.