Effect of Vitamin C in Autologous Stem Cell Transplantations (VICAST)

Randomized Controlled Trial on the Effect of Vitamin C Supplementation in Autologous Stem Cell Transplantations

In the study the investigators will randomize patients that receive an autologous stem cell transplantation for myeloma or lymphoma for treatment with vitamin C or placebo during 6 weeks. Primary endpoint will be immune recovery.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Myeloma Multiple
• Intervention / Treatment: Drug: Vitamin C; Drug: Placebos

Detailed Description

Rationale: Recent studies showed that ascorbic acid (AA) stimulates proliferation and maturation of T lymphocytes and natural killer (NK) cells. Chemotherapy results in depletion of those cells and thereby an increased infection rate. A pilot study showed low levels of AA in the plasma of several patients after chemotherapy followed by autologous stem cell transplantation for hematological malignancies. AA supplementation could be beneficial to the recovery of the immune system in these patients.

Objective: The aim of this study is to examine the effect of vitamin C supplementation on immune recovery in patients with autologous stem cell transplantation. The aim of the run-in phase of the study is to examine the effect of intravenous vitamin C supplementation on plasma concentrations of vitamin C in patients with autologous stem cell transplantation at day 14 in order to be sure that in the intervention study accurate AA plasma levels will be present.

Study design: run-in phase, followed by randomized controlled trial Study population: All participants will be adults (minimally 18 years old) that are planed to receive an autologous stem cell transplantation for multiple myeloma or lymphoma and are recruited at the MUMC+. In total there will be 3 expected (run-in phase) + 44 (randomized controlled trial) participants.

Main study parameters/endpoints: Primary endpoints will be AA plasma level on day 14 (run-in phase) and the day of neutrophil recovery after stem cell transplantation (randomized-controlled phase). Secondary endpoints will be AA leukocyte levels, infection rate, duration of hospital stay, side effects of chemotherapy, overall survival, coagulation parameters, platelet reactivity, fibrinolysis and quality of life.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

AA supplementation could be beneficial for the immune recovery in the participants of this study. The risks associated with participation in this study are low. Vitamin C supplementation is safe and hardly has any documented side effects.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands
      • MUMC+

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older
• written informed consent
• diagnosis of malignant lymphoma or multiple myeloma
• require chemotherapy plus autologous stem cell transplantation as standard of care for the disease at that stage
• central venous catheter in place or planned

Exclusion Criteria:

• inability to understand the nature and extent of the trial and the procedures required
• history of kidney stones
• kidney failure requiring dialysis or eGFR <30 mL/min. (CDK-EPI formula)
• history of G6PD deficiency
• life expectancy < 1 month
• use of immunosuppressive medication other than chemotherapy and corticosteroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vitamin C; vitamin C intravenous during hospitalization, followed with vitamin C oral	Drug: Vitamin C; vitamin C intravenous during hospitalization, after oral, total 6 weeks.; Other Names: ascorbic acid
EXPERIMENTAL: Placebo; placebo intravenous during hospitalization, followed with placebo oral	Drug: Placebos; placebo intravenous during hospitalization, after oral, total 6 weeks; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
immune recovery	the day of repopulation (return of neutrophil to at least 0.5 × 109/l) after autologous stem cell transplantation.	day 14-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AA plasma levels	AA plasma levels	day 14
AA leukocyte levels	AA leukocyte levels	day 14
Incidence of infections/ neutropenic fever	fever and infections during hospitalization	day 1-28
Days of hospitalization	number of days patients are admitted in our hospital	dag 1-28
Days with fever (≥ 38.5° C)	Amount of days admitted patients have a fever	day 1-28
Incidence of bloodstream infections	number of bloodstream infections of admitted patients	day1-28
Quality of life according to the EORTC QLQ-C30	quality of live questionaire	Day 0, day 14, day 42
Overall survival (3 months)	overall survival at 3 months	3 months
Relapse rates (3 months)	relapse rate at 3 months	3 months
Use of systemic antimicrobial agents (incidence and duration)	use of antibiotics during hospitalization	dau 1-28
platelet reactivity	platelet reactivity tests	day 10
ROS production	ROS production platelets	day 10
platelet mitochondrial dysfunction	platelet mitochondrial function test	day 10
number and severity of bleeding episodes during admission	number and severity of bleeding episodes during admission	day 1-28

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Gerard Bos, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 10, 2019
• Primary Completion (ACTUAL): March 1, 2022
• Study Completion (ACTUAL): March 1, 2022

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 24, 2019
• First Posted (ACTUAL): May 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: autologous stem cell transplantation; ascorbic acid; vitamin C; ascorbate
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: NL68010.068.18; 2018-004135-77 (EUDRACT_NUMBER)

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
• product manufactured in and exported from the U.S.: No