Overall study design
TNF-α
This study began with a laboratory experimental study on the validation and stability test of LL-37 in cream vehicle. It then proceeded with the randomized, double-blind controlled trial on the efficacy of LL-37 cream for DFU healing. The laboratory experimental study was conducted at Quality Testing Service Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok. The clinical trial was conducted at Outpatient Clinic of Internal Medicine Department, RSCM. Samples were analyzed at Eijkman Institute for Molecular Biology, while the levels of LL-37, IL-1α and TNF-α were measured at Integrated Laboratory Faculty of Medicine, Universitas Indonesia. Sample collection and data analysis for the clinical trial were conducted from January 2020 to June 2021. Randomization sequence was generated using a computer with a 1:1 allocation using random block sizes of 8. The LL-37 and placebo creams were prepacked in identical opaque jars and consecutively numbered for each participant. Determination of whether a participant would be treated with LL-37 cream (group A) or with placebo cream (group B) was prepared by a statistical supervisor with no clinical involvement in the trial and was unknown to any of the researchers. After a participant signed the consent form, they were assigned a prepacked jar on which the letter “A” or “B” was written. Both participants and researchers were kept blinded to the allocation of the treatment. This study was approved by the FKUI-RSCM Medical Research Ethical Committee in Jakarta and it complied with the Declaration of Helsinki guidelines. Written informed consent was obtained from every subject. They also signed informed consent regarding publishing their data and photographs. This trial is registered at ClinicalTrials.gov, number NCT04098562.