Clinical trial NCT06422741: Effect of a Grape Seed Proanthocyanidin Extract (GSPE) on LDL Cholesterol Levels in Rotating Night Shift Workers
Official title: Effect of a Grape Seed Proanthocyanidin Extract (GSPE) on LDL Cholesterol Levels in Rotating Night Shift Workers With Moderate Hypercholesterolemia. Randomized, Crossover, Controlled and Triple Blind Study.(CIRCAFENOL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiovascular Diseases
Circadian Rhythm Sleep Disorder, Shift Work Type
Cholesterol Level, High
Keywords: Proanthocyanidins
Circadian Rhythm
Metabolic Syndrome
Melatonin
Polyphenols
Lead sponsor: Fundació Eurecat
Sponsor class: OTHER
Collaborators: name: University Rovira i Virgili
First posted: 2024-05-21
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The physiological processes of the body present daily oscillations called circadian rhythm. The circadian rhythm is essential for maintaining the vital functions of organisms, intervening directly and indirectly in a multitude of key processes, such as hormone secretion, cycles of activity and rest throughout the day, body temperature, the metabolism or absorption, processing and detoxification of nutrients. There are factors such as certain work schedules, prolonged exposure to screens, certain eating patterns or social jetlag, which have a negative impact on the circadian rhythm, causing its disruption and favoring the appearance of health alterations. Thus, there is evidence that associates night shift work with a higher incidence of risk factors for developing metabolic syndrome and cardiovascular diseases, including obesity, elevated blood levels of glucose, triglycerides, and low-density lipoprotein cholesterol (LDL-C), as well as lower levels of high-density lipoprotein cholesterol (HDL-C). In addition, disorders in the sleep cycle are associated with the development of hypertension and type 2 diabetes.

Several previous studies show that a grape seed proanthocyanidin extract (GSPE) has beneficial effects on different parameters by restoring the circadian rhythm.

Detailed description: The main objective of the study is to evaluate the effect of daily GSPE intake, in combined with dietary recommendations, on LDL-C levels in individuals with rotating night shift work.

The secondary objectives are to evaluate the effects of GSPE on: anthropometric parameters,blood pressure, heart rate and endothelial function, markers of lipid and carbohydrate metabolism and insulin resistance, atherogenic indices, circulating levels of sex hormones and those related to hunger, satiety and stress; markers of systemic inflammation; circadian rhythm markers and sleep quality; level of physical activity, energy consumption, and changes in gene expression of key metabolic enzymes.

A randomized, crossover, placebo-controlled, triple-blind nutritional intervention study will be conducted. The study will be carried out in a population of 22 volunteers. Men and women aged 18 years or older, who are working a rotating night shift for at least 1 year and with blood levels of LDL-C between 116 and 190 mg/dL may participate.

Each volunteer will make 5 visits to the facilities of the EURECAT Nutrition and Health Technological Unit, in accordance with the study design:

* A pre-selection visit (to check inclusion/exclusion criteria), and if the inclusion criteria are met.
* Two study visits during consumption of the first product (GSPE or placebo), which will take place on the first day of study (visit 1) and after 6 weeks of treatment (visit 2).
* Two study visits during consumption of the second product (GSPE or placebo), which will take place after a three-week washout period (visit 3), and after 6 weeks of treatment (visit 4).

The main variable of the CIRCAFENOL study is circulating LDL-C levels.

Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 years or older.
* Follow a rotating night shift work schedule\* for at least one year before the start of the study.

  \* shift workers with at least 5 night shifts per month alternating with day and/or afternoon shifts, with a seniority equal to or greater than one year.
* Have no intention of changing the work shift during the course of the study.
* Circulating LDL-C levels between 116 -190 mg/dL\*, without pharmacological treatment with antihypertensives and/or lipid-lowering agents.

  \*Values of 116 to 190 mg/dl indicate moderate alteration in the lipid profile and a greater risk of suffering from cardiovascular diseases, according to the European Society of Cardiology, and the European Society of Atherosclerosis.
* Have signed the informed consent before starting the study.
* Know how to read, write and speak in Catalan or Spanish

Exclusion Criteria:

* BMI values \> 30 kg/m2
* Take supplements, multivitamin supplements (Vit.D, Vit. E and Vit.C), mineral supplements (Zinc, Selenium), essential fatty acids (omega-3), polyphenols, natural plant extracts, or phytotherapeutic products that interfere with the treatment under study.
* Consumption of alcoholic beverages:

  * Men: consume 4 or more Standard Beverage Units daily or 28 Standard Beverage Units weekly.
  * Women: Consume 2 or more Standard Beverage Units daily or 17 Standard Beverage Units weekly.
* Be an active smoker.
* Having lost more than 3 kg of weight in the last 3 months.
* Present food intolerances and/or allergies related to the study products, such as hypersensitivity to cellulose or proanthocyanidins.
* Present any chronic or autoimmune disease in clinical manifestation that may affect the results of the study such as diabetes (type I or II), cardiovascular disease, chronic kidney disease, hyper or hypothyroidism, chronic gastrointestinal diseases or cancer.
* Present familial hypercholesterolemia.
* Present hypertension (Systolic ≥140 mmHg; Diastolic ≥90 mmHg)
* Present any previous cardiovascular disease defined as myocardial infarction, angina pectoris, stroke or peripheral arterial disease.
* Individuals with treatment in the last 3 months before the start of the study with lipid-lowering, antidiabetic and/or antihypertensive drugs, or other drugs that may interfere with the results of the study.
* Taking supplements with polyphenol components or those aimed at lipid or blood pressure control in the last 3 months before the start of the study or during participation in the study.
* Follow a diet to lose weight, or very restrictive types of eating, such as intermittent fasting, ketogenic diet, etc.
* Being pregnant or intending to become pregnant.
* Being breastfeeding.
* Be participating or have participated in a clinical trial with medications or nutritional intervention study in the last 30 days before inclusion in the study.
* Suffering from eating disorders or psychiatric disorders.
* Being unable to follow study guidelines.

Primary outcomes:
measure: Change in LDL cholesterol levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
Secondary outcomes:
measure: Change in body weight.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Height.
timeFrame: At week 1.
measure: Change in BMI.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in waist circumference.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in conicity index.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in waist circumference to height ratio.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in the amount of body fat.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in the amount of muscle mass.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in the amount of bone mass.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in the amount of total body water.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in systolic blood pressure.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in diastolic blood pressure.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in resting heart rate.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in endothelial function.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum total cholesterol levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum HDL-c levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum Triglycerides levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in total cholesterol to HDL-c ratio.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in LDL-c to HDL-c ratio.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in Plasma atherogenic index.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum glucose levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum insulin levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum glycosylated hemoglobin levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in Homeostatic Model Assessment from Insulin Resistance Index (HOMA-IR).
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum high sensitivity c-reactive protein levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum ghrelin levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum leptin levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in circulating thyroid hormone T3 levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in circulating thyroid hormone T4 levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in circulating testosterone levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in circulating estrone levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in circulating 17-β-Estradiol levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in circulating estriol levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum melatonin levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in urine 6-Sulfatoxymelatonin levels.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in activity and rest cycles (subjective measurement).
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in activity and rest cycles (objective measurement).
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Pittsburgh Sleep Quality Index.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Chronotype.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in circulating GSPE metabolites.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in food consumption habits.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in Physical activity.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in body temperature.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in gene expression in peripheral blood mononuclear cells.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Change in serum metabolite profile.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Adverse events
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Consumption of dietary supplements.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Concomitant medication.
timeFrame: Before (baseline) and after treatment period (6 weeks) for each of the two treatments (GSPE and placebo).
measure: Age.
timeFrame: At week 1.
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Eurecat
state: Tarragona
city: Reus
country: Spain
facility: Fundació EURECAT
state: Tarragona
Study officials:
affiliation: UTNS (Eurecat, Reus)
name: Antoni Caimari Palou, PhD
role: PRINCIPAL_INVESTIGATOR
References: