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A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors

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Abstract

Aim

We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients.

Methods

This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II–IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA).

Results

The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial η2 = 0.333). The Nuvastatic™ group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial η2 = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial η2 = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen’s d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%).

Conclusion

Nuvastatic™ is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials.

Trial registration

ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11–05-2020.

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Data availability

Participant data and statistical analysis plan are illustrated in the Supplementary Material available with publication.

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Acknowledgements

We appreciate the support given by Dr. Sanghamitra Pati for reviewing the paper. We also thank Assoc. Prof. Dr Albiruni Abdul Razak from Princess Margaret Cancer Centre and Mount Sinai Hospital for editing the publication. We acknowledge Harvard Medical School faculty (GCSRT) for the overall study design and analysis and providing insightful and constructive comments.

Funding

The Malaysian Ministry of Agriculture (KP/ITTP/S/1/367–1 Jld.2 (91)) funded this work.

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Authors and Affiliations

Authors

Contributions

AMSAM, LCM designed the study protocol and secured study funding. ASAM, MASAA, MBKA, AG, FSRAS, KGB conducted the study, collected data, and performed patients’ follow-up. ASAM was a part of the trial management group and was the patient representative. LCM, MLN and AMSAM managed project administration. ASAM, VN, MBKA, FSRAS, MD, recruited participants. MD, CP, SSK, BSTNHS verified the data and performed the data analysis. ASAM and SMY wrote the first draft of the report with input from NML. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Corresponding author

Correspondence to Aman Shah Abdul Majid.

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Competing interests

The authors declare no competing interests.

Ethics approval

This study was conducted in accordance with the Declaration of Helsinki. All researchers / authors have read the Declaration of Helsinki developed by the World Medical Association (WMA).

Conflict of interest

AMSAM, ASAM, SSK, MNV, MBKA, and FSRAS have commercial interest in Nuvastatic™. All other authors declare no competing interests.

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Ng, M.L., Majid, A.M.S.A., Yee, S.M. et al. A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors. Support Care Cancer 32, 331 (2024). https://doi.org/10.1007/s00520-024-08536-w

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