Plant Stanol Esters and Preventing Asthma Symptoms

Study Overview
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Brief Summary
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Plant stanols are known to lower low-density lipoprotein cholesterol. However, studies have suggested that these compounds also influence the immune system. Asthmatic responses are predominantly T helper (Th)2 cell dependent, while plant stanols were previously found to activate Th1 cells and shift the immune response away from the Th2 cell dominant asthmatic response. The question now is whether this also translates into a reduction of clinical symptoms in asthma patients.The primary objective of this study is to demonstrate clinical benefits of prolonged consumption of plant stanols (delivered via plant stanol esters) in asthma patients. The secondary objectives are to evaluate the mechanisms via which plant stanols modulate the immune system and to evaluate the effects of plant stanol ester consumption on cardiovascular (CVD) risk parameters.

Official Title
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Plant Stanol Esters in the Prevention of Clinical Symptoms Related to Asthma: The PLANTASTIC Trial

Conditions
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Asthma, Allergic, Cardiovascular Diseases

Intervention / Treatment
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* Dietary Supplement: Soft chews containing 0.5g plant stanols (delivered as plant stanol esters)
* Dietary Supplement: Placebo soft chew


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with allergic asthma (GINA step 1-4) which is in a stable phase at the moment of inclusion (defined as no changes in asthma control and lung function in (at least) the past three months) Have been treated with prescribed asthma medication for at least one year Aged 18-70 years old BMI between 20 and 35 kg/m2 Willing to abstain from products containing plant sterols or stanols one month prior to the study (products with a cholesterol lowering claim of Becel ProActiv, Benecol, Danacol, store brands) Willing to abstain from products containing plant sterols or stanols during the study (products with a cholesterol lowering claim of Becel ProActiv, Benecol, Danacol, store brands) Willing to keep the intake of fish oil supplements constant Exclusion Criteria: Currently smoking or quitted smoking in the past year, with a maximum of 10 packyears as smoking history (packyears = packs per day * years of smoking) Allergy to an ingredient of the soft chews Suffering from inflammatory diseases (for CVD, illness must be minimally 3 years ago and currently under control in order to participate in the study) Fasting plasma glucose > 7.0 mmol/L Fasting serum TC > 8.0 mmol/L Having donated blood within one month prior to the start of the study, or planning to donate blood during the study Pregnant women Breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plant stanol group<br>This arm receives soft chews containing 0.5g of plant stanols (delivered as plant stanol esters). | Dietary Supplement: Soft chews containing 0.5g plant stanols (delivered as plant stanol esters)<br>* Soft chews containing 0.5g plant stanols delivered as plant stanol esters<br>|
| Placebo Comparator: Placebo group<br>This arm receives soft chews that do not contain 0.5g of plant stanols (delivered as plant stanol esters). | Dietary Supplement: Placebo soft chew<br>* Soft chew that does not contain plant stanols<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma control questionnaire score | The ACQ consists of seven questions: five questions are on asthma related symptoms, one on medication use and one on the FEV1. Participants are asked to score their symptoms and medication use of the past week on a scale from zero to six. The score of the ACQ is the average score on the seven questions. A score of zero means that asthma is fully controlled; a score of six means that asthma is severely uncontrolled. The minimal clinically important difference is 0.5. The ACQ has been validated and is widely use in research and clinical settings. | Change between T=0 months and T=12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma control questionnaire score | The ACQ consists of seven questions: five questions are on asthma related symptoms, one on medication use and one on the FEV1. Participants are asked to score their symptoms and medication use of the past week on a scale from zero to six. The score of the ACQ is the average score on the seven questions. A score of zero means that asthma is fully controlled; a score of six means that asthma is severely uncontrolled. The minimal clinically important difference is 0.5. The ACQ has been validated and is widely use in research and clinical settings. | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Forced expiratory volume in 1 second | Amount of air that can be exhaled forcefully in one second in Liters or % | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Forced vital capacity | Amount of air that can be exhaled forcefully in total in Liters or % | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Asthma related medication use | Self-reported medication use | Throughout 1 year | 
| Number of visits to the general practitioner or hospital | Self-reported amount of visits to the general practitioner or hospital | Throughout 1 year | 
| Incidence counts of exacerbations and other asthma related complaints | Self-reported amount of exacerbations and other asthma related complaints | Throughout 1 year | 
| Duration of exacerbations | Self-reported duration of exacerbations | Throughout 1 year | 
| Severity of exacerbations | Self-reported severity of exacerbations | Throughout 1 year | 
| Calculated disease load | Number x duration of exacerbations | Throughout 1 year | 
| Number of infections that occur throughout the study | Self-reported amount of infections | Throughout 1 year | 
| Leukocyte count | Number of leukocytes measured in EDTA plasma | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Leukocyte differential count | Number of subgroups of leukocytes measured in EDTA plasma | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Red blood cell count | Number of red blood cells measured in EDTA plasma | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Platelet count | Number of platelets measured in EDTA plasma | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Hematocrit | Hematocrit measured in EDTA plasma | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Hemoglobin | Hemoglobin measured in EDTA plasma | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Immune parameters (1) | Cytokine production by PBMCs after stimulation with antiCD3-antiCD28 antiCD28 antibodies using the TruCulture system | T=0 months, T=6 months, T=12 months | 
| Immune parameters (2) | Total IgE | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Immune parameters (3) | Total IgM | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Immune parameters (4) | hsCRP | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Fasted metabolism (1) | Serum lipid and lipoprotein profile | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Fasted metabolism (2) | Serum non-cholesterol sterols and stanols | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Fasted metabolism (3) | Plasma glucose metabolism | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Vascular function markers (1) | Carotid-femoral pulse wave velocity (PWV) | T=0 months and T=12 months | 
| Vascular function markers (2) | Pulse wave analysis (PWA) | T=0 months and T=12 months | 
| Vascular function markers (3) | Retinal microvascular caliber | T=0 months and T=12 months | 
| Cardiometabolic risk marker | Office blood pressure | T=0 months and T=12 months | 
| Cognitive function | CANTAB tests | T=0 months and T=12 months | 
| Anthropometry (1) | Body weight | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Anthropometry (2) | Height | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Anthropometry (3) | Body mass index | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Anthropometry (4) | Waist circumference | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Anthropometry (5) | Hip circumference | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Anthropometry (6) | Waist-to-hip ratio | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Quality of life score | 32-item questionnaire (including social, spiritual, emotional, cognitive, physical, activities of daily living, and integrated Quality of Life) | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Fatigue | Fatigue severity score (FSS), a 9-item questionnaire is used to determine the severity of fatigue a subject experienced in the past week during daily activities | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Physical activity | Baecke's questionnaire | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Mood | Affect grid | T=0 months, T=3 months, T=6 months, T=9 months, T=12 months | 
| Diet | Food frequency questionnaire is used to determine if the participants maintain their habitual diet and to determine if the participants do not consume plant stanols and/or sterols outside the intervention | T=0 months, T=6 months, T=12 months | 
| Immune cell characterisation | Fluorescence-activated cell sorting (FACS) | T=0 months, T=6 months, T=12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plant stanols, Asthma, Immune system, Metabolic health