Clinical trial NCT05030363: ALDH Enzyme in CRF With Advanced GI Cancer
Official title: The Efficacy and Safety of Alcoholic Dehydrogenase (ALDH) Enzyme Supplement in Chemotherapy-Related Fatigue With Advanced Gastrointestinal Cancer Patients: A 2-Period, Crossover, Single-Center Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Fatigue
Gastrointestinal Cancer
Aldehyde Dehydrogenase
Keywords: Chemotherapy-Related Fatigue
Gastrointestinal Cancer
Aldehyde Dehydrogenase
Lead sponsor: Korea University Anam Hospital
Sponsor class: OTHER
First posted: 2021-09-01
Enrollment: 82
Sex: ALL
Minimum age (years): 19
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A 2-Period, Crossover, Single-Center Study
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of FACIT-F score
timeFrame: Day 15 compared to baseline
Secondary outcomes:
measure: Change of FACIT-F score
timeFrame: Day 29 compared to day 15
measure: Change of ESAS
timeFrame: Day 15 compared to baseline
measure: Change of ESAS
timeFrame: Day 29 compared to day 15
measure: Incidence of treatment-related adverse events
timeFrame: Day 15 and 29
measure: Exploratory biomarker studies - Urine malondialdehyde - ALDH2 polymorphism (ALDH2 *1/*2, rs671 A/G) - Change of inflammatory cytokines
timeFrame: Day 1, 15 and 29
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
Study officials:
affiliation: Korea University Anam Hospital
name: Soohyeon Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: