Health-related Quality of Life-intervention in Survivors of Breast and Other Cancers Experiencing Cancer-related Fatigue Using Traditional Chinese Medicine: The HERBAL Trial (HERBAL)

Health-related Quality of Life-intervention in Survivors of Breast and Other Cancers Experiencing Cancer-related Fatigue Using Traditional Chinese Medicine: The HERBAL Trial

HEalth-Related Quality of Life-intervention in Survivors of Breast and Other Cancers Experiencing Cancer-related Fatigue Using TraditionAL Chinese Medicine: The HERBAL Trial

This study is a phase 2, randomized, double-blinded, placebo-controlled trial to evaluate the efficacy and safety of a Traditional Chinese Medicine decoction, the modified Xiang Bei Yang Rong Tang, in alleviating cancer related fatigue in cancer survivors.

Cancer-related fatigue (CRF) is a distressing, persistent and subjective sense of physical, emotional, or cognitive tiredness related to cancer or its treatment. Currently there is a lack of effective conventional pharmacological intervention for treating this condition. Traditional Chinese Medicine (TCM) could be alternative therapy for managing CRF. This study is a phase 2, randomized, double-blinded, placebo-controlled trial to examine the efficacy and safety of a TCM decoction, the modified Xiang Bei Yang Rong Tang (XBYRT) in alleviating CRF in cancer survivors. Study participants recruited from National Cancer Centre Singapore (NCCS) will be randomized to receive either the XBYRT or placebo decoction. Participants will take their assigned decoction daily for a duration of 8 weeks and will be assessed using patient reported outcome (PRO) questionnaires. PROs used are the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ 30) for QOL, the Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) for fatigue and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Version 3 for cognitive abilities. The changes in scores measured by these assessment tools will be compared between the XBYRT intervention and placebo groups. Blood biomarkers such as inflammatory cytokines, mitochondrial DNA and oxidative stress markers will also be evaluated in the study participants. Additionally, adverse events or serious adverse events in participants will be monitored for safety. Results from this study will provide a better understanding on the role of TCM in managing CRF.

Modified Xiang Bei Yang Rong Tang is a combination of 15 herbal components and it is available in granules form to be dissolved in hot water for consumption

Difference in Global Health Status (GHS) score from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) between XBYRT interventional and placebo arms from baseline to 8 weeks after baseline. The GHS scale ranges in score from 0-100. A higher score represents a better quality of life

Difference in MFSI-SF scores between XBYRT interventional and placebo arms. THE MFSI-SF consists of 30 items and has 5 subscales, each with 6 items: general fatigue, physical fatigue, emotional fatigue, mental fatigue, and vigour. The MFSI-SF measures different dimensions of fatigue, which can be combined to obtain an overall score. A higher score represents worse fatigue (total score ranges from -24 to 96)

Difference in FACT-Cog V3 scores between XBYRT interventional and placebo arms. FACT-Cog v.3 will be used to assess subjective cognitive disturbances. These disturbances are assessed via 33 items in the domains of concentration, functional interference, mental acuity, memory, multitasking and verbal fluency (total score ranges from 0-148). A lower score represents worse cognitive function.

Adverse events reported according to the Adverse events Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

Difference in EORTC QLQ-C30 scores between XBYRT interventional and placebo arms. The EORTC QLQ-C30 consists of 30 items across functional domains, symptoms domains and a global health status domain. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high level of functioning. A high score for a symptom scale represents a high level of problems.

Oxidative stress markers : malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)

Inclusion Criteria: Age ≥21 years Clinically diagnosed cancer (Stages I-III) Completed surgery/chemotherapy/radiotherapy for at least 1 month At least one month after starting on aromatase inhibitors or ovarian suppression for breast cancer survivors Not expected to receive surgery/chemotherapy/radiotherapy next 10 weeks Fatigue screening score ≥4 for past 7 days Life expectancy ≥3 months Patients satisfy TCM syndrome differentiation as qi and blood deficiency Experience 2 major symptoms coupled with typical tongue and pulse conditions; 2 major symptoms and 1 possible symptom coupled with tongue and pulse conditions; 1 major symptom and at least 2 possible symptoms coupled with tongue and pulse conditions Able to read and understand English or Mandarin Exclusion Criteria: Cancer recurrence and/or metastasis Untreated co-morbidities causing fatigue (e.g. Severe anaemia, thyroid disorder) On medications that cause fatigue (e.g. beta blockers) Patients on warfarin Cancer survivors receiving adjuvant therapy during the study period. Aromatase inhibitors and anti-HER2 monoclonal antibodies are acceptable. Receiving or planning to receive treatment from other TCM practitioners during the study period Breast feeding or intending to conceive/get pregnant during the study treatment period Patients who present with yin deficiency and deficiency syndromes (e.g. phlegm-dampness, blood stasis, toxic-heat and qi stagnation)

Yap NY, Loo WS, Zheng HF, Tan QM, Tan TK, Quek LYP, Tan CJ, Toh YL, Ng CC, Ang SK, Tan VKM, Ho HK, Chew L, Loh KW, Tan TJY, Chan A. A study protocol for HEalth-Related quality of life-intervention in survivors of Breast and other cancers experiencing cancer-related fatigue using TraditionAL Chinese Medicine: the HERBAL trial. Trials. 2020 Nov 4;21(1):909. doi: 10.1186/s13063-020-04810-4.