ALDH Enzyme in CRF With Advanced GI Cancer (ALDHCRF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Fatigue; Gastrointestinal Cancer; Aldehyde Dehydrogenase
• Intervention / Treatment: Drug: ALDH enzyme supplementation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Soohyeon Lee, M.D., Ph.D.; Phone Number: 82-2-920-5690; Email: soohyeon_lee@korea.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 02841
    • Recruiting
    • Korea University Anam Hospital
    • Contact: Soohyeon Lee, M.D., Ph.D.; Email: soohyeon_lee@korea.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Upfront ALDH enzyme supplement; Upfront ALDH enzyme supplement; After randomization, patients will receive ALDH enzyme supplement twice a day for consecutive 14 days during chemotherapy (period 1; day 1 to day 14) until unacceptable toxicity, or consent withdrawal. Patients will visit clinic on day 15, then will be followed on day 29 without ALDH enzyme administration during subsequent chemotherapy (period 2).	Drug: ALDH enzyme supplementation; ALDH enzyme (PICOZYMEQ™)
Other: Delayed ALDH enzyme supplement; Delayed ALDH enzyme supplement; patients will not take ALDH enzyme supplement during chemotherapy after randomization on day 1 to day 14 (period 1). On day 15, Patients will visit for subsequent chemotherapy and start ALDH enzyme supplement twice a day for 14 consecutive days during chemotherapy (period 2; day 15 to day 29).	Drug: ALDH enzyme supplementation; ALDH enzyme (PICOZYMEQ™)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of FACIT-F score	Change of FACIT-F score on day 15 compared to baseline after chemotherapy	Day 15 compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of FACIT-F score	Change of FACIT-F score on day 29 compared to day 15 after chemotherapy	Day 29 compared to day 15
Change of ESAS	Change of ESAS on day 15 compared to baseline after chemotherapy	Day 15 compared to baseline
Change of ESAS	Change of ESAS on day 29 compared to day 15 after chemotherapy	Day 29 compared to day 15
Incidence of treatment-related adverse events	Safety and tolerability assessments	Day 15 and 29
Exploratory biomarker studies - Urine malondialdehyde - ALDH2 polymorphism (ALDH2 *1/*2, rs671 A/G) - Change of inflammatory cytokines	Analysis Inflammatory cytokine and metabolites during ALDH enzyme supplement and explore predictive biomarker using urine malondialdehyde	Day 1, 15 and 29

Collaborators and Investigators

• Sponsor: Korea University Anam Hospital
• Investigators: Principal Investigator: Soohyeon Lee, MD, PhD, Korea University Anam Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Anticipated): August 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 24, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Gastrointestinal Cancer; Chemotherapy-Related Fatigue; Aldehyde Dehydrogenase
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Fatigue; Gastrointestinal Neoplasms
• Other Study ID Numbers: PicoEnTech001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No