Adjunctive Intravenous Ascorbic Acid for Advanced Non-Small Cell Lung Cancer (AIVAA)

Adjunctive Intravenous Ascorbic Acid for Advanced Non-Small Cell Lung Cancer: A Double Blind, Placebo Controlled, Phase II Randomized Controlled Trial

This is a two arm RCT evaluating the effect of intravenous vitamin C versus placebo in patients with incurable non-small cell lung cancer. Participants in both arms will be receiving platinum doublet chemotherapy with or without concurrent immunotherapy as standard care. We plan to enroll 90 patients over 5 years.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Ascorbic acid; Other: Normal Saline

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dugald Seely, ND, MSc; Phone Number: 2 613-792-1222; Email: dseely@thechi.ca
• Study Contact Backup: Name: Mark Legacy, BSc, CCRP; Phone Number: 1 613-792-1222; Email: mlegacy@thechi.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • Recruiting
      • The Ottawa Hospital
      • Contact: Paul Wheatley-Price, MD; Email: pwheatleyprice@toh.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults (≥18 years of age) seen at TOHCC with stage IIIB or IV primary non-small cell lung cancer
2. Eligible and scheduled for first line platinum-doublet chemotherapy with or without concurrent immunotherapy

Exclusion Criteria:

1. ECOG status greater than 2
2. Previously received IVC within 6 months prior to randomization
3. Biochemical deficiency in G6PD
4. Estimated Glomerular Filtration Rate (eGFR) less than 45 mL/min
5. Currently taking insulin or warfarin
6. History of severe renal dysfunction or hemochromatosis
7. Previously undergone cytotoxic chemotherapy or immunotherapy within 12 months prior to randomization
8. If pregnant or planning to become pregnant: not a carrier of the gene for G6PD deficiency
9. Currently taking an investigational product or participation in an investigational study within the past 30 days
10. Any reason which, under the discretion of the Principal Investigator or delegate, would preclude the patient from participating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Vitamin C; 1g/kg IVC administered twice weekly for 6 months.	Drug: Ascorbic acid; High dose ascorbic acid delivered intravenously; Other Names: Vitamin C
Placebo Comparator: Normal Saline; Equivalent volume normal saline administered twice weekly for 6 months.	Other: Normal Saline; 0.9% NaCl solution; Other Names: Sodium Chloride Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life	Participant reported quality of life (QOL) measured using the Functional Assessment of Cancer Therapy - Lung (FACT-L). FACT-L is a validated tool for assessing QOL in patients with lung cancer. FACT scores are normalized to values between 0-100, where 0 is the worst QOL and 100 is the best QOL imaginable. Each chemotherapy cycle is 3 weeks in length.	Baseline, Chemo cycles 1-4, 6 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	The incidence of all cause mortality will be compared between arms.	24 months
Chemotherapy-Related Toxicities	Frequency of adverse events (AE) which are commonly experienced by patients undergoing chemotherapy. Measured using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). 31 symptoms were selected by the investigators.	12 months
Frequency of Discontinuation of Chemotherapy	Patients often discontinue chemotherapy due to side effects. The investigators will monitor the incidence of stopping chemotherapy and compare the number of patients who stop chemotherapy in both arms.	6 months
Change in General Symptom Burden	Measured using the Edmonton Symptom Assessment Scale, which measures 9 symptoms commonly experienced by cancer patients. Each symptom is rated on a scale of 0-10, where 0 is the best symptom and 10 is the worst symptom. Each chemotherapy cycle is 3 weeks in length.	Baseline, chemo cycles 1-4, 6 months, 12 months
Change in C-Reactive Protein Levels	The investigators will monitor the changes in C-reactive protein (CRP), a common indicator of systemic inflammation. Mean changes in CRP will be compared between arms. Each chemotherapy cycle is 3 weeks in length.	Baseline, chemo cycles 1-4, 6 months, 12 months
Tumour Progression	The investigators will monitor tumour progression using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, which measures the incidence of complete response, partial response, stable disease, and progressive disease during treatments.	12 months
Safety	The investigators will monitor the incidence of all adverse events in both arms to add to the safety profile of IVC in this population.	6 months
Cytotoxicity	The investigators will assess the ability of IVC to bring serum ascorbate levels to at least 15mM, which is the hypothesized level at which cytotoxic effects may occur. Levels 15mM or above will be considered adequate.	12 months

Collaborators and Investigators

• Sponsor: The Canadian College of Naturopathic Medicine
• Collaborators: Ottawa Hospital Research Institiute

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2031

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Organic Chemicals; Pharmaceutical Preparations; Carbohydrates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Sodium Compounds; Chlorides; Hydrochloric Acid; Ascorbic Acid; Saline Solution; Sodium Chloride
• Other Study ID Numbers: 20220721-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with other researchers. Cumulative data not present in the manuscript or on this website may be shared upon request.

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