Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05840848
Other study ID # AZ: F-2017-039
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date November 21, 2017
Est. completion date June 1, 2018

Study information

Verified date May 2023
Source University of Hohenheim
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

In vitro studies found supplemental levels of iron and zinc to inhibit the micellization and cellular uptake of β-carotene. Here, we investigated this in vivo, in a double-blind 3-arm crossover human trial. Healthy males (n=6) ingested, with breakfast, a single dose of 15 mg β-carotene in combination with either a placebo, 25 mg iron or 30 mg zinc capsule. Blood samples were collected at baseline and hourly for 10 hours. The triacylglycerol-rich fraction (TRF) was analysed for concentrations of β-carotene and plasma for β-carotene, retinol, triacylglycerols, LDL- and HDL-cholesterol.


Description:

The study followed a double-blind crossover design with three study arms separated by one week washout periods. In short, the participants were asked to follow a diet low in carotenoids by avoiding all orange, yellow, red and green fruits and vegetables for four days. This was followed by three days of a strictly carotenoid-free diet, which only allowed foods from a specified list (Supplemental Table A2). On each study day, β-carotene was administered in the morning after a >10 hour overnight fast (Supplemental Figure A1). All participants orally ingested, in random order, a single dose of 15 mg β-carotene (BIOVEA) with either a placebo (empty capsule), 25 mg iron (FeSO4; Woerwag Pharma GmbH & Co. KG, Boeblingen, Germany) or 30 mg zinc (ZnSO4; Woerwag Pharma) capsule. A standardised dinner was provided on the evening before the trial and standardised meals were provided during the entire intervention day (Supplemental Table A3). On the first study day, the amount of food (weight or volume) consumed by each participant for each meal was recorded and the same amounts provided during the following two arms to ensure similar food consumption, especially of fat. Water was available unrestricted for consumption throughout the day. Blood samples were drawn from an indwelling venous cannula and collected at 0 hours directly before β-carotene supplementation and then every hour for 10 hours. For the determination of plasma concentrations of β-carotene, LDL- and HDL-cholesterol, and triacylglycerols (TAG), blood was collected in tubes containing EDTA (Sarstedt AG & Co, Nuebrecht, Germany) and immediately centrifuged (3000 × g, 10 min, 4 °C). From the obtained plasma samples, three aliquots were stored at -80 °C until further analysis and the rest ultracentrifuged to obtain the triacylglycerol-rich fraction (TRF). For the analyses of liver and kidney function markers, plasma and serum were obtained from blood sampled at the 0- and 4-hour time points. The TRF was prepared according to [10]. Briefly, plasma (3.5 mL) was transferred to an ultracentrifuge tube and carefully overlaid with 8 mL 1.3% sodium chloride and then ultracentrifuged (Beckman Coulter, OptimaTM L-80 XP Ultracentrifuge) using a swinging bucket rotor (SW41Ti) at 150 000 x g for 1 hour at 4 °C. Afterwards, the TRF was isolated by transferring the upper ~6 mL, which was then overlaid with nitrogen gas to minimize oxidation and stored at -80 °C until extraction. The plasma samples were randomly extracted and analysed by HPLC according to [15]. Briefly, 40 µL plasma was extracted with an ethanol/n-butanol mixture (50:50) containing apo-80-carotenal-methyloxime (12µL/100 mL; Fluka Analytical (Merck Group KGaA), Darmstadt, Germany) as internal standard. After centrifugation, the clear supernatant was analysed by HPLC. The TRF was extracted and analysed by HPLC [15]. For the extraction, 100 µl apo-80-carotenal-methyloxime (12 µL/100 mL) and 2 mL ethanol (for deproteination) were added to 3 mL of the TRF and vortexed for 30 sec. The solution was extracted twice with 2 mL hexane. The hexane layers were removed, combined and evaporated in a centrifugal vacuum concentrator (Christ, RVC 2-25 CD plus) and the dried sample re-dissolved in 100 µL acetonitrile and immediately analysed by HPLC. Both the plasma and TRF samples were analysed using a Shimadzu HPLC (LC-10AD) equipped with a UV-Vis detector (SPD 20A, set at 450 nm). Carotenoids were separated using a ReproSil 80 ODS-2 column (3 µm, 250 x 4.6 mm; Dr. Maisch GmbH, Ammerbuch, Germany) and an eluent in recirculation mode (82% acetonitrile, 15% 1,4-dioxin, and 3% methanol (vol/vol) containing 100 mM ammonium acetate and 10 mM triethylamine) at a flow rate of 1.5 mL/min [15]. A β-carotene standard (≥97.0% purity, Sigma-Aldrich) was used to construct a standard curve. Plasma TAG, HDL- and LDL-cholesterol were analysed by a clinical laboratory (Laborärzte Sindelfingen, Sindelfingen, Germany).


Recruitment information / eligibility

Status Completed
Enrollment 12
Est. completion date June 1, 2018
Est. primary completion date December 14, 2017
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 18 Years to 50 Years
Eligibility Inclusion Criteria: - Male - aged 18 and 50 years Exclusion Criteria: - overweight (BMI >25 kg/m2), - metabolic and endocrine diseases, - drug abuse, - use of dietary supplements, - us of any form of medication, - smoking, - frequent alcohol consumption (>20 g ethanol/day), - adherence to a restrictive dietary regimen, - physical activity of more than 5 h/wk, - participation in a clinical trial within the past 3 months prior to recruitment, - a known intolerance against ß-carotene, iron and/or zinc supplements.

Study Design


Related Conditions & MeSH terms


Intervention

Dietary Supplement:
Control beta-carotene supplement plus Placebo
15 mg beta-carotene supplement from BIOVEA consumed before breakfast together with an empty capsule.
Control beta-carotene supplement plus iron Supplement
15 mg Beta-carotene supplement from BIOVEA consumed before breakfast together with 25 mg iron (FeSO4; Woerwag Pharma GmbH & Co. KG, Boeblingen, Germany)
Control beta-carotene supplement plus zinc Supplement
15 mg Beta-carotene supplement from BIOVEA consumed before breakfast together with 30 mg zinc (ZnSO4; Woerwag Pharma GmbH & Co. KG, Boeblingen, Germany)

Locations

Country Name City State
Germany University of Hohenheim Stuttgart Baden-Württemberg

Sponsors (1)

Lead Sponsor Collaborator
University of Hohenheim

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary TRF B-carotene B-carotene concentration in the triacylglycerol-rich fraction of the plasma 10 hours
Primary Plasma B-carotene B-carotene concentration int he plasma 10 hours
Secondary Plasma LDL-cholesterol LDL-cholesterol concentration in Plasma 10 hours
Secondary Plasma HDL-cholesterol HDL-cholesterol concentration in Plasma 10 hours
Secondary Plasma TAG triacylglycerol concentration in Plasma 10 hours
Secondary liver function markers ?-GT, AST, ALT, Alkaline phosphatase and Bilirubin measured 4 hours
Secondary Kidney funtion markers Creatinine i.S. and Uric acid measured 4 hours
See also
  Status Clinical Trial Phase
Completed NCT06043739 - Relative Bioavailability and Effect of Food Study With an Oral Mini-tablet Formulation of Filgotinib in Healthy Subjects Phase 1
Completed NCT02557139 - Bioavailability of Belumosudil (KD025) in Healthy Male Subjects Phase 1
Completed NCT02010944 - A Study to Compare How Much Solifenacin Succinate and Mirabegron Reach the Blood When Administered Together as Fixed-dose Combination Tablets and With Single Individual Tablets of the Same Medications at Three Dose Levels Phase 1
Completed NCT01208155 - Study in Healthy Males to Assess Bioavailability of 4 Different Fostamatinib Tablets Phase 1
Not yet recruiting NCT01136551 - Comparative Bioavailability Study of an Immediate Release and Controlled Release Oral Formulations of Huperzine A N/A
Completed NCT04097808 - Impact of the Source and Food Matrices on the Bioavailability of Peptan® (Collagen Peptides) in Healthy Subjects N/A
Active, not recruiting NCT06098001 - Bioavailability Study of Hemp Phenolics N/A
Completed NCT01912144 - Absorption of Phenolic Acids From Coffee in Humans N/A
Completed NCT03915626 - Effect of Heat on Rivastigmine TDS Products Early Phase 1
Completed NCT01464450 - Pharmacokinetics Study of Oral Rivaroxaban in Healthy Participants Phase 1
Completed NCT01448772 - Comparative Bioavailability of Dronabinol Oral Solution Versus Branded Capsule 5 mg Under Fasting Conditions Phase 1
Completed NCT01181973 - Safety, Tolerability and Relative Bioavailability of Pegvisomant in Healthy Subjects Phase 1
Completed NCT00858767 - Arabic Gum-Absorption Study N/A
Completed NCT04113564 - Absolute Oral Bioavailability of Remimazolam Phase 1
Completed NCT04645394 - Bioavailability of Anthocyanins From Aronia Extract in Healthy Men - a Pilot Study N/A
Completed NCT03485885 - Bioavailability of Maqui Berry Extract (MBE) in Healthy Subjects
Completed NCT02986529 - A Study to Assess the Bioavailability of Oral Sodium Oligo-mannurarate (GV-971) in Healthy Chinese Male Subjects Phase 1
Completed NCT01789359 - Urinary Excretion of Anthocyanins During Long Term Blueberry Feeding N/A
Completed NCT01638143 - Bio-equivalence Study N/A
Completed NCT00755872 - Assess the Influence of a High-fat Meal on the Relative Bioavailability Of Two Formulations of Risedronate Phase 1