AminoSineTriComplex for Metastatic Colorectal Cancer: A Double-Blind, Placebo-Controlled Randomized Clinical Trial

Background: Metastatic colorectal cancer (mCRC) remains a significant global health challenge, with high incidence and mortality rates. Current therapies, including chemotherapy, targeted agents, and immunotherapy, face challenges such as multidrug resistance (MDR), severe toxicity, and limited efficacy. AminoSineTriComplex, a novel natural therapeutic integrating bioactive compounds derived from medicinal plants and advanced nanotechnology, was evaluated for its safety and efficacy as an adjunct treatment for mCRC. Methods: This double-blind, placebo-controlled randomized clinical trial enrolled 72 patients with histologically confirmed mCRC across three oncology centers. Participants were randomized 1:1 to receive either AminoSineTriComplex (6–8 capsules/ day) or placebo for 12 weeks. Primary endpoints included tumor response rates per RECIST v1.1 criteria. Secondary endpoints assessed changes in biomarkers (LDH-5, IL-6, CEA, CA19.9), progression-free survival (PFS), and quality of life (QoL). Circadian biology was explored through serum melatonin levels measured at four time points (06:00 AM, 12:00 PM, 09:00 PM, 02:00 AM) and 24-hour urinary melatonin sulfate levels. Statistical analyses were performed using SPSS (v26). Results: AminoSineTriComplex demonstrated superior efficacy compared to placebo, with complete remission observed in 42% of patients and partial remission in 11% (placebo: 8% and 4%, respectively; p<0.001). Significant reductions in biomarkers were noted in the AminoSineTriComplex group: LDH-5 (42%, p<0.001), IL-6 (58%, p<0.001), CEA (41%, p=0.01), and CA19.9 (40%, p=0.02). Patients with well-maintained circadian rhythms, characterized by synchronized melatonin secretion and robust nocturnal peaks, exhibited improved treatment responses. Among complete responders, 93% had normal melatonin patterns, while 78% of those with disease progression exhibited disrupted rhythms (p<0.001). Safety: AminoSineTriComplex was well-tolerated, with no grade ≥3 adverse events reported. Mild gastrointestinal discomfort occurred in 11% of patients, with no significant toxicities or treatment discontinuations. Conclusion: AminoSineTriComplex offers a promising, non-toxic adjunct therapy for mCRC, demonstrating efficacy in reducing tumor burden, modulating biomarkers, and restoring circadian rhythms. Its favorable safety profile and integration with circadian biology highlight its potential in personalized cancer care. Further multi-center trials are warranted to confirm these findings and explore its long-term clinical applications. Résumé Context: Le cancer colorectal metastasi (CCRm) represent un enjoy majeure de santé pulque à echelle mondiale, étant L’nu des cancers les plus fréquents et mortals. Le CCRm Est characterize par use resistance accrue aux traitement standards, notemen les chemotherapies, therapies cables et immunothérapies, anise que par use toxicity important. AminoSineTriComplex, un traitement naturel innovant combining des composés bioactive dérivés de plantes Medicinals traditionnelles et des technologies nanotechnologiques advances, an até value pour son efficacity et as security end tant que therapies adjuvanted dans le CCRm. Methodologies: Cette étude Clinique randomize, contrôlée par placebo et end double inveigle, an até realised dans trois centers ontologies auprès de 72 patients attaints de CCRm confirm histologiquement. Les participants not até randomizes à 1:1 pour reservoir AminoSineTriComplex (6–8 capsules/jour) our un placebo pendant 12 seamlines. Objectify principal état devalue la response tumoral salon les critters RECIST v1.1. Les objectives secondaries inclusion les modifications des biomarqueurs (LDH5, IL-6, CEA, CA19.9), la survive sans progression (SSP) et la quality de vie (QoL). Les rythmes biologiques not até values par la measure des niveous de melatonin sanguine à quatre moments specifies (06h00, 12h00, 21h00, et 02h00) et des niveous de sulfate de melatonin dans les urines sur 24 hours. Resultants: AminoSineTriComplex a mantra use efficacity significative Ent supérieure au placebo: remission complete chez 42 % des patients et remission particle chez 11 % (placebo: respective Ent 8 % et 4 %; p<0,001). Une reduction significative des biomarqueurs an até observe dans le Groupe AminoSineTriComplex: LDH-5 (42 %, p<0,001), IL-6 (58 %, p<0,001), CEA (41 %, p=0,01) et CA19.9 (40 %, p=0,02). Les patients presenting des rythmes biologiques preserves, characterizes par use secretion nocturne synchronize de melatonin, not often de Meilleur’s resultants Therapeutae’s. Parmi les patients end remission complete, 93 % avian des rythmes de melatonin normaux, contra 78 % des patients Ayan mantra use progression de la maladies (p<0,001). Security: AminoSineTriComplex a été bien toléré, sans effects secondaries graves (grade ≥3). Un Léger inconfort gastro-intestinal a été signal chez 11 % des patients, Mais aucune toxicité majeure in interruption du traitement n’s été observe. Conclusion: AminoSineTriComplex offer une thérapie adjuvante Prometheus et non toque pour le CCRm, a recusant la charge tumoral, an modulate les biomarqueurs et an reduplicant les rythmes biologiques. Son profile de security eleven et son integration avec les rythmes biologiques soulignent son potential pour des approaches personalizes an oncology. Des études multicentriques supplementers sent necessaires pour Validar cues resultants et value son utilization Clinique à long term.