Clinical trial NCT03964688: Effect of Vitamin C in Autologous Stem Cell Transplantations
Official title: Randomized Controlled Trial on the Effect of Vitamin C Supplementation in Autologous Stem Cell Transplantations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myeloma Multiple
Lymphoma
Keywords: vitamin C
ascorbate
ascorbic acid
autologous stem cell transplantation
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2019-05-28
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind placebo-controlled randomized trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: immune recovery
timeFrame: day 14-28
Secondary outcomes:
measure: AA plasma levels
timeFrame: day 14
measure: AA leukocyte levels
timeFrame: day 14
measure: Incidence of infections/ neutropenic fever
timeFrame: day 1-28
measure: Days of hospitalization
timeFrame: dag 1-28
measure: Days with fever (≥ 38.5° C)
timeFrame: day 1-28
measure: Incidence of bloodstream infections
timeFrame: day1-28
measure: Quality of life according to the EORTC QLQ-C30
timeFrame: Day 0, day 14, day 42
measure: Overall survival (3 months)
timeFrame: 3 months
measure: Relapse rates (3 months)
timeFrame: 3 months
measure: Use of systemic antimicrobial agents (incidence and duration)
timeFrame: dau 1-28
measure: platelet reactivity
timeFrame: day 10
measure: ROS production
timeFrame: day 10
measure: platelet mitochondrial dysfunction
timeFrame: day 10
measure: number and severity of bleeding episodes during admission
timeFrame: day 1-28
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: MUMC+
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: Gerard Bos
role: PRINCIPAL_INVESTIGATOR
References: