VitD: Vitamin D and Pre Cachexia and Cancer Cachexia in Epithelial Ovarian Cancer

Sponsor

Indonesia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04864431

Collaborator

Dharmais National Cancer Center Hospital (Other)

Enrollment

Locations

Arms

23.6

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Several ex vivo, in vitro, and observational studies on various type of cancer shown positive effect of vitamin D. Vitamin D has widely known as immunomodulator property in various diseases. However, it remains limited studies on immunity and cachexia in cancer, particularly in ovarian cancer. This study will investigate the effect of vitamin D in immune response during chemotherapy among epithelial ovarian cancer patients who have a low level of vitamin D and cachexia

Condition or Disease	Intervention/Treatment	Phase
Epithelial Ovarian Cancer	Dietary Supplement: Vitamin D Other: Placebo	N/A

Detailed Description

Studies result from laboratory suggested that vitamin D inhibit cancer cell proliferation and upregulate apoptosis pathway. Data from observational and ecology studies showed the inverse relationship between level of vitamin D and cancer risk. Clinical trials on colorectal, prostate, and breast cancer suggested that vitamin D had positive effect and improved clinical markers.

Vitamin D may alter immune response through regulation on cytotoxic CD8 T-lymphocyte and reduce pro inflammatory cytokines. High level of interleukin-6 and other cytokines in cancer may decrease lymphocyte T activity, resulting lowering effect of immune response.

This clinical trial will enroll 54 adults with newly diagnosed epithelial ovarian cancer patients. Following receive of informed consent, they will randomly allocated to receive whether vitamin D 2000 IU or placebo during chemotherapy period (6 cycles).

Subjects will fill out questionnaire on their first visit as well as each chemotherapy cycle (each month). Questionnaire will ask about demographic data, meal intake, sun exposure, and cachexia questionnaire (based on Cachexia Score). Subjects will also be examined on their physical status, anthropometry (weight, height, waist circumference), as well as body composition (fat mass, fat free mass, fat free mass index, phase angle).

Blood samples will be drawn from peripheral vein and sent to National Cancer Referral Hospital laboratory to measure 25(OH)D level, interleukin-6, CD8 cytotoxic level, CD8 cytotoxic activity, and circulating tumor cells. Blood collection will be done on the first visit, 3rd cycle of chemotherapy, and last cycle of chemotherapy. Subjects will be given their samples result during follow-up visit.

Vitamin D3 (Prove D3®) is donated from PT. Kalbe Farma. Departement of Medicine Physic Indonesia University as the third party which provides randomization and capsules containing vitamin D and placebo. Randomization key will be opened by the third party after finishing statistical data analysis. This study is being submitted a grant from Kalbe-BRIN.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Intervention group: vitamin D 2000 IU ; Control group: placeboIntervention group: vitamin D 2000 IU ; Control group: placebo

Masking:

Double (Participant, Investigator)

Masking Description:

Neither do investigator nor participants will not know the random allocation

Primary Purpose:

Treatment

Official Title:

The Effect of Vitamin D on Factors Contributing Pre Cachexia and Cachexia, a Study on Epithelial Ovarian Cancer

Actual Study Start Date :

Jan 12, 2022

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Vitamin D group Daily vitamin D3 2000 IU on day 1 through day 180 Intervention: vitamin D3 2000 IU	Dietary Supplement: Vitamin D Vitamin D capsules: each capsule contain 2 tablets of vitamin D 1000 IU. One capsule will be taken on day 1 through 180 Other Names: cholecalciferol
Placebo Comparator: Control group Daily placebo (saccharum lactis) on day 1 through day 180 Intervention: placebo	Other: Placebo Placebo capsule: Each capsule contain saccharum lactis. One capsule will be taken on day 1 through 180

Arm

Intervention/Treatment

Active Comparator: Vitamin D group

Daily vitamin D3 2000 IU on day 1 through day 180 Intervention: vitamin D3 2000 IU

Dietary Supplement: Vitamin D

Vitamin D capsules: each capsule contain 2 tablets of vitamin D 1000 IU. One capsule will be taken on day 1 through 180

Other Names:

cholecalciferol

Placebo Comparator: Control group

Daily placebo (saccharum lactis) on day 1 through day 180 Intervention: placebo

Other: Placebo

Placebo capsule: Each capsule contain saccharum lactis. One capsule will be taken on day 1 through 180

Outcome Measures

Primary Outcome Measures

Rate of immune response in participants receiving vitamin D change from baseline as assessed by lymphocyte CD8 [6 months]
lymphocyte CD8 is measured by flowcytometry

Secondary Outcome Measures

Find the change of vitamin D level [6 month]
vitamin D level is measured by Electro-Chemiluminescence Immunoassay (e CLIA). The normal range is 30-100 ng/ml
Find the daily intake of vitamin D from food [1 month]
The amount of vitamin D intake from food in one month is analyzed using food frequency questionnaire in microgram unit measurement. To find the daily intake from food is calculated the total intake in 1 month divided by 30 days. Recommended daily allowance of vitamin D intake from food is 15 microgram/day
Find the rate of sun exposure [1 week]
sun exposure defined as total duration of sun exposure per day. It assessed using "sun exposure questionnaire". It is calculated based on time outdoor multiply by amount of skin exposure (face, hand, arm, leg, sun bathing), added up everyday for one week. The minimum score is 0 and the maximum score is 56. No score is defined as either adequate or inadequate exposure
Effect of vitamin D in lowering inflammation [6 months]
defined inflammation as interleukin-6 which is measured by enzyme-linked immunosorbent assay in ng/ml unit measurement. Interleukin-6 increases if the level more than 4 pg/ml
Effect of vitamin D in lowering circulation tumor cells (CTC) [6 months]
the number of tumor cells in blood. Positive CTC if there are 5 tumor cells in 7,5 ml of blood
Effect of vitamin D in improving staging of cachexia [6 month]
a diagnostic tools for staging cachexia is measured by Cachexia Score (CASCO). The components of CASCO are body weight loss and composition, inflammation/metabolic disturbances, physical performance, anorexia, and quality of life. CASCO score is presented by numerical scale and classified as mild (score 0-25), moderate (26-50), severe (51-75), and terminal (76-100)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

age 18-60 years old who are newly diagnosed with ovarian cancer based on histopathology
epithelial ovarian cancer stage II-III
haven't received chemotherapy
pre-cachexia or cachexia
level of vitamin D below 30 ng/ml
no vitamin D allergy
ability and willingness to understand and provide informed consent

Exclusion Criteria:

autoimmune disease
chronic liver disease
chronic renal disease
known had hypercalcemia
refractory cachexia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cipto Mangunkusumo Hospital	Jakarta	DKI Jakarta	Indonesia	13430
2	Tarakan Hospital	Jakarta Pusat	Jakarta	Indonesia	13430
3	Dharmais National Cancer Hospital	Jakarta		Indonesia	13430