Clinical trial NCT06471023: A Pharmacokinetic Study of Single Oral Doses of Six Different Vitamin C Product Forms
Official title: A Randomized, Crossover, Pharmacokinetic Assessment of Single Oral Doses of Six Different Vitamin C Product Forms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Pharmacokinetic
Keywords: Vitamin C
Ascorbic acid
Pharmacokinetics
Lead sponsor: DSM Nutritional Products, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
First posted: 2024-06-24
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Vitamin C (ascorbic acid) is an essential nutrient linked to many aspects of basic human physiology. It is a potent antioxidant and involved as a cofactor for many human enzymes, and its extreme deficiency can lead to a fatal disease known as scurvy and reduce immune function. Relatively less serious deficiency over a longer period of time may also increase cardiovascular disease and cancer risk. Deficiency is common amongst the Canadian general population, with around 5.5% being found to possess deficient plasma concentrations. Moreover, amongst many industrialized countries, rates of deficiency can be as high as 15% of the general population. Potential vitamin C overdose is not considered to be serious, but symptoms can include nausea, vomiting, headache, rash, and asthenia.

The pharmacokinetic profiles of vitamin C supplements are influenced by their formulation, impacting safety and efficacy. The study will compare the PK properties of six different vitamin C formulations, each over a 24 h test period.

Detailed description: This is a randomized, 6-way crossover pharmacokinetic study to assess 6 different vitamin C formulations in healthy adults.

There is 1 comparator product (CP), 1 reference product (RP), and 4 test products (TP: TP1, TP2, TP3, TP4):

* TP1 (Vitamin C formulation 1, 1000 mg)
* TP2 (Vitamin C formulation 2, 1000 mg)
* TP3 (Vitamin C formulation 3, 1000 mg)
* TP4 (regular Vitamin C mega dose, 3000 mg)
* CP (Vitamin C formulation 4, 1000 mg)
* RP (regular Vitamin C, 1000 mg)

Each sequence will have 9 participants for a total of 27 participants.

* Sequence 1: TP1 → TP2 → TP3 → TP4 → CP → RP
* Sequence 2: RP → TP1 → TP2 → TP3 → TP4 → CP
* Sequence 3: CP → RP → TP1 → TP2 → TP3 → TP4

Pharmacokinetic blood sampling will occur pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10 and 24 h post dose. Blood samples collected will be used to assess the PK profiles of all 6 formulations. PK parameters measured will include AUC0-24, Cmax, Tmax, AUCinf, T1/2, and Kel for L-ascorbic acid. L-ascorbic acid concentrations will be measured in urine to compare excretion during 0-4 h, 4-8 h, 8-10 h, and 10-24 h post-dose between all 6 formulations. L-ascorbic acid will also be measured in peripheral blood mononuclear cells at 8 h and 24 h post-dose to compare uptake and maintenance between all 6 formulations.

Gastrointestinal symptom questionnaire scores and total antioxidant capacity in plasma at 24 hours post-dose will also be compared between all 6 formulations.

Safety endpoints will be assessed throughout the study and will include reports of adverse events, vital signs, and safety laboratory assessments.

Eligibility criteria: Inclusion Criteria:

* In good general health (i.e., no uncontrolled diseases or conditions) as deemed by the investigator.
* Are able to swallow the study products, in whole.
* Have a body mass index (BMI) between 18.0 to 29.9 kg/m2 (inclusive).
* Must have suitable veins for repeated venipuncture.
* No nicotine and/or nicotine products, including smoking or vaping of any kind (e.g., cigarettes) for at least 3 months before screening.
* Have maintained consistent dietary habits (including supplement intake) and lifestyle for the last 3 months before screening. Participants must be willing to maintain these habits throughout the duration of the study, with the exception of changes required by the vitamin C dietary restrictions.
* Willing to comply with the vitamin C dietary restrictions, 2 weeks prior to the baseline and throughout the duration of the study until the last study visit.
* Agree to follow the restrictions on concomitant treatments as listed in the protocol.
* Agree to follow the restrictions on lifestyle as listed in the protocol.
* Agree to use acceptable contraceptive methods as listed in the protocol.
* Willing and able to agree to the requirements of this study, willing to give voluntary consent, able to understand and read the questionnaires, and carry out all study-related procedures.
* Agrees not to donate blood until 3 months after study completion
* Must weigh ≥ 58.9 kg (130 lbs) at screening

Exclusion Criteria:

* Individuals who are lactating, pregnant or planning to become pregnant during the study.
* Have a known sensitivity, intolerability, or allergy to any of the study products or their excipients.
* Have Type I diabetes, Type II diabetes, high blood pressure (≥140 systolic or ≥90 diastolic mmHg), or thyroid disease.
* Have medical condition(s) known to interfere with absorption, distribution, metabolism, or excretion of the study product (e.g., Crohn's disease, short bowel, acute or chronic pancreatitis, or pancreatic insufficiency).
* Have a history of heart disease, renal or hepatic impairment/disease, gout, hemochromatosis, glucose-6-phosphate dehydrogenase deficiency, immune disorders and/or immunocompromised (i.e., HIV/AIDS).
* Have a history of cancer (except localized skin cancer without metastases or in situ cervical cancer), unless a minimum of 5 years before the screening visit have elapsed since full recovery.
* Reports a clinically significant illness during the 28 days before the first dose of study product, including acute inflammatory conditions or viral infections (e.g., cold, flu, COVID-19), or any other condition that, in the opinion of the investigator, may be of a concern for the study.
* Participants must not exceed the ''high'' physical activity level as defined by the International Physical Activity Questionnaire-- Short Form (IPAQ-SF) in the week prior to baseline and agree to adhere to this requirement throughout the study duration. A 'high' physical activity level is defend as having engaged in vigorous-intensity physical activity on at least 3 days achieving a total of 1500 or more Metabolic Equivalent of Task (MET)-minutes per week; or, having engaged in any combination of walking, moderate-intensity, or vigorous-intensity physical activities on 7 or more days achieving a total of 3000 or more MET-minutes per week.
* Reports a significant blood loss or blood donation totaling between 101 mL to 449 mL of blood within 30 days prior to the first PK visit or a blood donation of more than 450 mL within 3 months prior to the first PK visit.
* Major surgery in 3 months before screening or planned major surgery during the study.
* Are receiving treatments for or have been hospitalized in the last 12 months for psychiatric disorders (e.g., depression, bipolar disorder, schizophrenia, etc.).
* Demonstrates a positive urine drug screen for compounds listed in the protocol, or positive breath alcohol test at screening or baseline.
* Have a history of alcohol or substance abuse in the 12 months before screening (including having been hospitalized for such in an in-patient or out-patient intervention program).
* Currently consumes, on average, more than 2 standard alcoholic beverages a day or has any habit of alcohol use that, to the opinion of the investigator, may be of a concern for the study. A standard alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of liquor.
* Current enrolment or past participation in another study with any product(s) with at least one active ingredient within 30 days before first dose of study product (or screening) or longer, if the previous test product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study.
* Any other medical condition/situation or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to participate in the study or its measures or pose a significant risk to the participant.

Primary outcomes:
measure: Bioavailability of vitamin C compared between each of the liposomal formulations TP1 and TP2 to the traditional RP
timeFrame: 0-24 hours
Secondary outcomes:
measure: Pharmacokinetics (PK) of single doses of six vitamin C formulations
timeFrame: 0-24 hours
measure: Pharmacokinetics (PK) of single doses of six vitamin C formulations
timeFrame: 0-24 hours
measure: Bioavailability of vitamin C compared between six different formulations.
timeFrame: 0-24 hours
measure: Excretion of vitamin C in urine over a 24 h period compared between six different formulations.
timeFrame: 0-24 hours
measure: Uptake and maintenance of vitamin C in peripheral blood mononuclear cells (PBMCs) between six different formulations.
timeFrame: 0-24 hours
Other outcomes:
measure: Pharmacokinetics (PK) of single doses of six vitamin C formulations.
timeFrame: 0-24 hours
measure: Pharmacokinetics (PK) of single doses of six vitamin C formulations.
timeFrame: 0-24 hours
measure: Pharmacokinetics (PK) of single doses of six vitamin C formulations.
timeFrame: 0-24 hours
measure: Gastrointestinal tolerability of single doses of six vitamin C formulations.
timeFrame: 0-24 hours
measure: Antioxidant effects of six different vitamin C formulations.
timeFrame: 0-24 hours
measure: Heart rate
timeFrame: 0-24 hours
measure: Systolic and diastolic blood pressure
timeFrame: 0-24 hours
measure: Incidence of adverse events
timeFrame: up to 8 weeks
measure: Whole blood hemoglobin
timeFrame: 24 hours
measure: Whole blood hematocrit
timeFrame: 24 hours
measure: Whole blood white blood cells
timeFrame: 24 hours
measure: Whole blood neutrophils
timeFrame: 24 hours
measure: Whole blood eosinophils
timeFrame: 24 hours
measure: Whole blood basophils
timeFrame: 24 hours
measure: Whole blood lymphocytes
timeFrame: 24 hours
measure: Whole blood monocytes
timeFrame: 24 hours
measure: Whole blood mean platelet volume
timeFrame: 24 hours
measure: Whole blood platelet count
timeFrame: 24 hours
measure: Whole blood red blood cell count
timeFrame: 24 hours
measure: Whole blood red blood cell distribution width
timeFrame: 24 hours
measure: Whole blood mean corpuscular volume
timeFrame: 24 hours
measure: Whole blood mean corpuscular hemoglobin
timeFrame: 24 hours
measure: Whole Blood Mean Corpuscular Hemoglobin Concentration
timeFrame: 24 hours
measure: Serum Sodium
timeFrame: 24 hours
measure: Serum Potassium
timeFrame: 24 hours
measure: Serum Chloride
timeFrame: 24 hours
measure: Serum Urea
timeFrame: 24 hours
measure: Serum Creatinine
timeFrame: 24 hours
measure: Serum Estimated Glomerular Filtration
timeFrame: 24 hours
measure: Serum Total Protein
timeFrame: 24 hours
measure: Serum Albumin
timeFrame: 24 hours
measure: Serum Globulin
timeFrame: 24 hours
measure: Serum Total Bilirubin
timeFrame: 24 hours
measure: Serum Glucose
timeFrame: 24 hours
measure: Serum Alanine Transaminase
timeFrame: 24 hours
measure: Serum Aspartate Transaminase
timeFrame: 24 hours
measure: Serum Alkaline Phosphatase
timeFrame: 24 hours
measure: Gamma Glutamyl Transferase
timeFrame: 24 hours
Locations:
city: Guelph
country: Canada
facility: Nutrasource Site (Apex Trials)
state: Ontario
Study officials:
References: