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Effectiveness of Vitamin E and Hydrogen-Rich Water on Radiation Therapy-Induced Adverse In Patients With Rectal Cancer

Primary Purpose

Radiation-induced Injuries in Patients With Rectal Cancer

Status
Unknown status
Phase
Phase 3
Locations
Palestinian Territory, occupied
Study Type
Interventional
Intervention
Vitamin E
Hydrogen rich water
placebo
Sponsored by
University of Jordan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Radiation-induced Injuries in Patients With Rectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • - Men or women.
  • Older than 18 years.
  • Histologically proven adenocarcinoma of the rectum.
  • Underwent radiotherapy.
  • Absence of any psychological, and sociological condition that potentially affects the compliance with the study protocol and follow-up schedule.

Exclusion Criteria:

  • The use of anticoagulant and antiplatelet agents.
  • Any disease of disorder capable of contraindicating the absorption of Vitamin E or Hydrogen water in the body of a patient being investigated.
  • No known history of problems absorbing fats (e.g., Crohn disease, cystic fibrosis)

Sites / Locations

  • Augusta Victoria HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

vitamin E

Hydrogen rich water

placebo

Arm Description

Oral intake of Vitamin E treatment will be given on a daily basis in a single-blind manner one day before the first day of RT and continued for 8 weeks. Patients in the group receiving 500 IU of d-alpha-tocopherol capsules orally (3 times daily).

Oral intake of HRW (2 ppm) treatment will be given on a daily basis in a single-blind manner one day before the first day of RT and continued for 8 weeks. The group of patients receiving Hydrogen water took an amount of 250 ml orally 3 times a day.

Oral intake of placebo will be given on a daily basis in a single-blind manner one day before the first day of RT and continued for 8 weeks. The placebo group received 3 soft gel placebo capsules containing gelatin three times a day.

Outcomes

Primary Outcome Measures

total blood count
A hematology analyzer is commonly used to investigate changes in hematological parameters, which vary in response to systemic changes. These hematological parameters include WBCs, which defend the body against foreign invaders; their numbers increase during inflammation. RBCs contain hemoglobin, which carries oxygen to the tissues. Platelets have a hemostatic function. During injury, they gather at the site of damage in blood vessels and form a primary platelet plug. Bleeding occurs when the platelet count decreases.
Nuclear factor erythroid 2-related factor 2 (Nrf2)
Nrf2, a basic leucine-zipper containing transcription factor that plays a key role in the regulation of the production and expression of antioxidant genes in the body. Nrf2 usually combines with the ARE, which is the upstream promoter region of SOD, CAT, GPx, etc. After combination, the enzyme complex upregulate the expression of a serious endogenous protective antioxidant genes in the tissue, thereby maintaining the balance of oxidation and antioxidant levels of the cells.
Superoxide dismutases (SOD)
SODs are a group of metalloenzymes that are found in all kingdoms of life. SODs form the front line of defense against reactive oxygen species (ROS)-mediated injury. These proteins catalyze the dismutation of superoxide anion free radical (O2-) into molecular oxygen and hydrogen peroxide (H2O2) and decrease O2- level which damages the cells at excessive concentration. This reaction is accompanied by alternate oxidation-reduction of metal ions present in the active site of SODs. During oxidative damage, the level of this enzyme within the tissues is elevated in order to protect them. SOD converts O2- into H2O2.
Catalase (CAT)
CAT is a common enzyme found in nearly all living organisms, which are exposed to oxygen. The first function assigned to catalase is the transformation of hydrogen peroxide into oxygen and water. It thus plays an important role in defending cells against oxidative damage by degrading hydrogen peroxide. Catalase can modulate the growth rate by various mechanisms, the first obviously being its ability to detoxify H2O2. The second is its ability to bind and protect certain proteins from potential oxidative damage, which in turn are involved in the processes of proliferation and migration. As shown by many reports, catalase and mitochondrial superoxide dismutase control cell growth and migration processes in cancer cells.
Glutathione S-transferase (GST)
GST isoenzyme superfamilies detoxify a wide-range of toxic chemicals and environmental substances are extensively expressed in mammalian tissues. GSTs play a key role in the deactivation of reactive oxygen species (ROS) and the metabolism of lipids, chemotherapeutic agents. GSTs are mainly involved in conjugation of reduced glutathione (GSH) with diverse substrates specificity and it is possible that genetic variations in these enzymes will influence cellular response to the environmental agents. GSTs are overexpressed in response to a chemical or oxidative stress as an adaptive physiology and upregulated in cancerous state of organ or tissue. GSTs are essentially involved in susceptibility to various forms of cancer as they are vital in detoxification mechanism to metabolize the environmental carcinogens.
Malondialdehyde (MDA)
MDA is one of the consequences of uncontrolled oxidative stress is cells, tissues, and organs injury caused by oxidative damage. It has long been recognized that high levels of free radicals or reactive oxygen species (ROS) can inflict direct damage to lipids. MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs, through enzymatic or nonenzymatic processes. MDA is highly reactive, capable of inhibiting enzymes that protect cells against the harmful effects of oxidative stress.
Tumor necrosis factors (TNF)
TNF refer to a group of cytokines which are mainly secreted by monocytes/macrophages. While it was first recognized for its anti-tumor activity, TNF has since been identified as a highly pleiotropic cytokine that mediates multiple cellular processes including inflammation, cell differentiation, cell survival and proliferation, and apoptosis. The master pro-inflammatory cytokine, TNF, has been shown to modulate multiple signaling pathways, with wide-ranging downstream effects. TNF plays a vital role in the typical immune response through the regulation of a number of pathways encompassing an immediate inflammatory reaction with significant innate immune involvement as well as cellular activation with subsequent proliferation and programmed cell death or necrosis.
Matrix metalloproteinases(MMPs)
MMPs are members of metzinc in group of zinc dependent endopeptidases which are responsible for degrading and remodeling of extracellular matrix (ECM) during organogenesis, wound healing, angiogenesis, apoptosis, cell proliferation and cancer progression. The expression and activity of MMPs in adult tissues is normally quite low, but increases significantly in various pathological conditions that may lead into unwanted tissue destruction, such as inflammatory diseases, tumour growth and metastasis. MMPs are produced by multiple tissues and cells. MMPs are secreted by connective tissue, pro-inflammatory, and uteroplacental cells.

Secondary Outcome Measures

Full Information

First Posted
January 13, 2021
Last Updated
February 14, 2021
Sponsor
University of Jordan
Collaborators
Slovak Academy of Sciences, Al-Quds University
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1. Study Identification

Unique Protocol Identification Number
NCT04713332
Brief Title
Effectiveness of Vitamin E and Hydrogen-Rich Water on Radiation Therapy-Induced Adverse In Patients With Rectal Cancer
Official Title
Effectiveness of Vitamin E and Molecular Hydrogen-Rich Water on Radiation Therapy-Induced Adverse In Adult Patients With Rectal Carcinoma in Al-Quds, Palestine
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
July 6, 2019 (Actual)
Primary Completion Date
March 8, 2021 (Anticipated)
Study Completion Date
May 8, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Jordan
Collaborators
Slovak Academy of Sciences, Al-Quds University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

Brief Summary
Controlled studies investigating the effects of vitamin E or H2 water or comparing their effectiveness on radiation therapy-induced injuries in RC patients are generally lacking. The present study hypothesis the following: (1) Pre - radiation therapy administration of vitamin E to patients with rectal carcinoma will provide radioprotection for exposed healthy tissues. (2) Consumption of H2 water by patients with rectal carcinoma undergoing RT will reduce the side effects of this modality. (3) Rectal cancer patients receiving H2 water will show better biological improvement than those receiving only vitamin E, i.e., H2 water is more effective antioxidant than vitamin E. (4) The proposed radiation countermeasures will not compromise the anti-tumor effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Radiation-induced Injuries in Patients With Rectal Cancer

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
vitamin E
Arm Type
Active Comparator
Arm Description
Oral intake of Vitamin E treatment will be given on a daily basis in a single-blind manner one day before the first day of RT and continued for 8 weeks. Patients in the group receiving 500 IU of d-alpha-tocopherol capsules orally (3 times daily).
Arm Title
Hydrogen rich water
Arm Type
Active Comparator
Arm Description
Oral intake of HRW (2 ppm) treatment will be given on a daily basis in a single-blind manner one day before the first day of RT and continued for 8 weeks. The group of patients receiving Hydrogen water took an amount of 250 ml orally 3 times a day.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Oral intake of placebo will be given on a daily basis in a single-blind manner one day before the first day of RT and continued for 8 weeks. The placebo group received 3 soft gel placebo capsules containing gelatin three times a day.
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin E
Other Intervention Name(s)
500 IU of d-alpha-tocopherol
Intervention Description
Members of the vitamin E family are hydrophobic fat-soluble compounds found in a variety of food sources such as vegetable oils, fruits, and vegetables consumed through diet. Vitamin E exists in 8 isoforms, a, b, g, d-tocopherol, and a, b, g, d-tocotrienol. The recommended daily allowance for adults is 15 mg per day for alpha-tocopherol, an amount which is easily met by dietary sources, and 30 mg per day for synthetic all-rac-alpha-tocopherol. The upper limit for intake is 1,000 mg per day. Very often, the dosage of vitamin E is given in international units (IU) as capsules, with a typical dose being 400 IU per day, which is above the recommended daily allowance. The health benefits of consuming vitamin E through diet or supplementation are believed to be for its antioxidant properties as a peroxyl radical scavenger. Vitamin E protects cells from cell damage caused by free radicals that damage cell membranes through lipid oxidation leading to DNA damage and cancer development.
Intervention Type
Dietary Supplement
Intervention Name(s)
Hydrogen rich water
Intervention Description
Molecular hydrogen is a new medical gas that can be dissolved in water and administered through drinking, inhalation, baths, intravenous drip. A growing body of evidence indicates that hydrogen, as a novel antioxidant, scavenges hydroxyl radical and peroxynitrite. In contrast to other antioxidants, gaseous molecular hydrogen efficiently penetrates cytoplasmic membranes and targets intracellular organelles, largely owing to its small size and neutral electricity. Thus, hydrogen has been suggested as a suitable candidate for the therapeutic strategies for various diseases, including certain types of cancer. Hydrogen has emerged as a promising cancer remedy as a preventative agent or in combined therapy with anticancer drugs. Hydrogen water consumption might mitigate the side effects of anticancer drugs by decreasing oxidative stress and ameliorating metamorphosis due to decreased apoptosis.
Intervention Type
Dietary Supplement
Intervention Name(s)
placebo
Intervention Description
Placebo containing gelatin is made by cooking down the protein collagen found in the skin, hooves, connective tissues, and bones of animals. The cooking process breaks down the bonds between proteins to make smaller, more bioavailable building blocks that your body can easily absorb. Like collagen, gelatin is packed with beneficial amino acids, especially the anti-aging superstar's glycine and proline, which are lacking in the standard Western diet. These amino acids make gelatin especially powerful for healing skin, gut, and joint damage. Because collagen and gelatin come from the same source, they have identical amino acid profiles
Primary Outcome Measure Information:
Title
total blood count
Description
A hematology analyzer is commonly used to investigate changes in hematological parameters, which vary in response to systemic changes. These hematological parameters include WBCs, which defend the body against foreign invaders; their numbers increase during inflammation. RBCs contain hemoglobin, which carries oxygen to the tissues. Platelets have a hemostatic function. During injury, they gather at the site of damage in blood vessels and form a primary platelet plug. Bleeding occurs when the platelet count decreases.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure
Title
Nuclear factor erythroid 2-related factor 2 (Nrf2)
Description
Nrf2, a basic leucine-zipper containing transcription factor that plays a key role in the regulation of the production and expression of antioxidant genes in the body. Nrf2 usually combines with the ARE, which is the upstream promoter region of SOD, CAT, GPx, etc. After combination, the enzyme complex upregulate the expression of a serious endogenous protective antioxidant genes in the tissue, thereby maintaining the balance of oxidation and antioxidant levels of the cells.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure
Title
Superoxide dismutases (SOD)
Description
SODs are a group of metalloenzymes that are found in all kingdoms of life. SODs form the front line of defense against reactive oxygen species (ROS)-mediated injury. These proteins catalyze the dismutation of superoxide anion free radical (O2-) into molecular oxygen and hydrogen peroxide (H2O2) and decrease O2- level which damages the cells at excessive concentration. This reaction is accompanied by alternate oxidation-reduction of metal ions present in the active site of SODs. During oxidative damage, the level of this enzyme within the tissues is elevated in order to protect them. SOD converts O2- into H2O2.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure
Title
Catalase (CAT)
Description
CAT is a common enzyme found in nearly all living organisms, which are exposed to oxygen. The first function assigned to catalase is the transformation of hydrogen peroxide into oxygen and water. It thus plays an important role in defending cells against oxidative damage by degrading hydrogen peroxide. Catalase can modulate the growth rate by various mechanisms, the first obviously being its ability to detoxify H2O2. The second is its ability to bind and protect certain proteins from potential oxidative damage, which in turn are involved in the processes of proliferation and migration. As shown by many reports, catalase and mitochondrial superoxide dismutase control cell growth and migration processes in cancer cells.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure
Title
Glutathione S-transferase (GST)
Description
GST isoenzyme superfamilies detoxify a wide-range of toxic chemicals and environmental substances are extensively expressed in mammalian tissues. GSTs play a key role in the deactivation of reactive oxygen species (ROS) and the metabolism of lipids, chemotherapeutic agents. GSTs are mainly involved in conjugation of reduced glutathione (GSH) with diverse substrates specificity and it is possible that genetic variations in these enzymes will influence cellular response to the environmental agents. GSTs are overexpressed in response to a chemical or oxidative stress as an adaptive physiology and upregulated in cancerous state of organ or tissue. GSTs are essentially involved in susceptibility to various forms of cancer as they are vital in detoxification mechanism to metabolize the environmental carcinogens.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure
Title
Malondialdehyde (MDA)
Description
MDA is one of the consequences of uncontrolled oxidative stress is cells, tissues, and organs injury caused by oxidative damage. It has long been recognized that high levels of free radicals or reactive oxygen species (ROS) can inflict direct damage to lipids. MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs, through enzymatic or nonenzymatic processes. MDA is highly reactive, capable of inhibiting enzymes that protect cells against the harmful effects of oxidative stress.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure
Title
Tumor necrosis factors (TNF)
Description
TNF refer to a group of cytokines which are mainly secreted by monocytes/macrophages. While it was first recognized for its anti-tumor activity, TNF has since been identified as a highly pleiotropic cytokine that mediates multiple cellular processes including inflammation, cell differentiation, cell survival and proliferation, and apoptosis. The master pro-inflammatory cytokine, TNF, has been shown to modulate multiple signaling pathways, with wide-ranging downstream effects. TNF plays a vital role in the typical immune response through the regulation of a number of pathways encompassing an immediate inflammatory reaction with significant innate immune involvement as well as cellular activation with subsequent proliferation and programmed cell death or necrosis.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure
Title
Matrix metalloproteinases(MMPs)
Description
MMPs are members of metzinc in group of zinc dependent endopeptidases which are responsible for degrading and remodeling of extracellular matrix (ECM) during organogenesis, wound healing, angiogenesis, apoptosis, cell proliferation and cancer progression. The expression and activity of MMPs in adult tissues is normally quite low, but increases significantly in various pathological conditions that may lead into unwanted tissue destruction, such as inflammatory diseases, tumour growth and metastasis. MMPs are produced by multiple tissues and cells. MMPs are secreted by connective tissue, pro-inflammatory, and uteroplacental cells.
Time Frame
One day before the first day of radiation exposure (initial data) and 2, 6 and 8 weeks post radiation exposure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Men or women. Older than 18 years. Histologically proven adenocarcinoma of the rectum. Underwent radiotherapy. Absence of any psychological, and sociological condition that potentially affects the compliance with the study protocol and follow-up schedule. Exclusion Criteria: The use of anticoagulant and antiplatelet agents. Any disease of disorder capable of contraindicating the absorption of Vitamin E or Hydrogen water in the body of a patient being investigated. No known history of problems absorbing fats (e.g., Crohn disease, cystic fibrosis)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ziad Abuawad, PhD candidate
Phone
00970598966442
Email
ziad_252002@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Musa Numan, Professor
Organizational Affiliation
The University of Jordan
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jan Slezak, Professor
Organizational Affiliation
The Slovak Academy of Sciences
Official's Role
Study Chair
Facility Information:
Facility Name
Augusta Victoria Hospital
City
E. Jerusalem
Country
Palestinian Territory, occupied
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Atif Rimawi, PhD
Phone
00972547951918
Email
ati_rimawi@yahoo.comf

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effectiveness of Vitamin E and Hydrogen-Rich Water on Radiation Therapy-Induced Adverse In Patients With Rectal Cancer

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