Effect of Vitamin C in Autologous Stem Cell Transplantations

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Myeloma Multiple, Lymphoma

Intervention / Treatment
-----------------
* Drug: Vitamin C
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double blind placebo-controlled randomized trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin C<br>vitamin C intravenous during hospitalization, followed with vitamin C oral | Drug: Vitamin C<br>* vitamin C intravenous during hospitalization, after oral, total 6 weeks.<br>* Other names: ascorbic acid;|
| Experimental: Placebo<br>placebo intravenous during hospitalization, followed with placebo oral | Drug: Placebos<br>* placebo intravenous during hospitalization, after oral, total 6 weeks<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vitamin C, ascorbate, ascorbic acid, autologous stem cell transplantation