Aldehyde Dehydrogenase, Fatigue, Gastrointestinal Cancer
Conditions
Keywords
Chemotherapy-Related Fatigue, Gastrointestinal Cancer, Aldehyde Dehydrogenase
Brief summary
Aldehyde dehydrogenase (ALDH) enzyme supplementation plays an essential role in the elimination of toxic metabolites and reduction of reactive oxygen species bioactivation, which can protect and relieve chemotherapy-related fatigue (CRF) in cancer patients. The aim of this study is to evaluate the efficacy and safety of ALDH enzyme in CRF with advanced gastrointestinal cancer patients. The primary endpoint is the change of FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue) score on day 15 compared to baseline after chemotherapy. The secondary endpoint including change of FACIT-F on day 29 compared to day 15, change of ESAS (Edmonton Symptom Assessment System) on day 15 compared to baseline, safety and toxicities, and exploratory biomarkers.
Detailed description
Chemotherapy-related fatigue (CRF) occurs universally in cancer patients which can be a debilitating symptom that affects patients' quality of life. The impact of CRF has been associated with mood disorder, sleep disturbance, cognitive dysfunction, inflammation mediated putative biological disturbances, and functional morbidities. Although the etiology is heterogeneous and complex, one of the proposed mechanisms is that chemotherapy induced multiple oxidative degradation of the lipid membrane which generates reactive oxygen species (ROS) and tissue damage. These conditions result in inflammation-induced reduction in central dopaminergic neurotransmission, nutritional deficiency (especially in vitamins and minerals), and immunodeficiency, which clinically manifest as CRF. To date, various agents including psychostimulants (methylphenidate, donepezil, and modafinil), dexamethasone, and Korean red ginseng (KRG) were used in the management of CRF. However, the prevalence of CRF is still high primarily due to lack of proven effective therapies. ALDH enzyme supplementation plays an essential role in the eliminates 4-hydoxynonenal, malondialdehyde from lipid peroxidation and reduce ROS bioactivation, which can protect and relieve CRF in cancer patients. Based on these rational backgrounds, the aim or this study is to evaluate the efficacy and safety of ALDH enzyme in CRF with advanced gastrointestinal cancer patients.
Interventions
DRUGALDH enzyme supplementation
ALDH enzyme (PICOZYMEQ™)
Sponsors
Korea University Anam Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Masking description
Open label
Intervention model description
A 2-Period, Crossover, Single-Center Study
Eligibility
Sex/Gender
ALL
Age
19 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
To be included in the trial, subjects must meet all of the following criteria: 1. Fatigue score ≥ 4 on analog scale of 0 to 10 (0; not at all, 10; worst possible fatigue) for more than 1 week. 2. Subject has willing and able to written informed consent form (ICF) prior to any screening procedures. 3. Age ≥ 19 years old of male and female. 4. Life expectancy more than 3 months.
Exclusion criteria
1. Hb \< 8g/dL 2. Uncontrolled hyper- or hypothyroidism despite of appropriate treatment 3. Evidence of central nervous system (CNS) tumor metastasis; permitted if asymptomatic or neurologically stable. 4. Sign of active and uncontrolled bacterial or viral infection requiring systemic therapy 5. Abnormal cognition status or psychiatric disease. 6. Anamnesis of hypersensitivity reaction to the ALDH enzyme. 7. Current use or previous use within 14 days of the following medications: Korean-Chinese medications, methylphenidate, modafinil, phenobarbital, diphenylhydantoin, primidone, phenylbutazone, monoamine oxidase inhibitors, clonidine, and tricyclic antidepressants. 8. Medical conditions that could affect trial outcomes or subjects who were considered unsuitable for trial enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of FACIT-F score | Day 15 compared to baseline | Change of FACIT-F score on day 15 compared to baseline after chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of FACIT-F score | Day 29 compared to day 15 | Change of FACIT-F score on day 29 compared to day 15 after chemotherapy |
| Change of ESAS | Day 15 compared to baseline | Change of ESAS on day 15 compared to baseline after chemotherapy |
| Incidence of treatment-related adverse events | Day 15 and 29 | Safety and tolerability assessments |
| Exploratory biomarker studies - Urine malondialdehyde - ALDH2 polymorphism (ALDH2 *1/*2, rs671 A/G) - Change of inflammatory cytokines | Day 1, 15 and 29 | Analysis Inflammatory cytokine and metabolites during ALDH enzyme supplement and explore predictive biomarker using urine malondialdehyde |
Countries
South Korea
Contacts
Primary ContactSoohyeon Lee, M.D., Ph.D.
Outcome results
None listed