Clinical trial NCT04641494: The Effect of CLA on Obesity, Lung Functions, Lipid Profile and Inflammation in Women With BMI≥25
Official title: The Effect of 12 Weeks of Conjugated Linoleic Acid on Obesity Markers, Lung Functions, Lipid Profile and Inflammation in Overweight and Obese Women: Double-blind Randomised Control Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Lung Functions
Inflammation
Lipid Disorder
Keywords: Conjugated linoleic caid
Obesity
Lung functions
Inflammation
heat shock proteins
Adhesion molecules
Lead sponsor: University of Chester
Sponsor class: OTHER
First posted: 2020-11-23
Enrollment: 58
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Conjugated linoleic acid or CLA, is one of the food supplements that could be found in meat, fats, and dairy products of ruminants which has been fed grass not on grains. CLA has shown anti-cancer, anti-obesity, and anti-inflammatory effects in several animal modules, but the results of the human studies were not consistent. Also, a very limited number of studies looked at the CLA effect on the respiratory system. The study will look at the effect of 12 weeks of supplementation of conjugated linoleic acid on obesity markers, lung functions, lipid profile, and inflammation in overweight and obese women in a double-blind randomized control trial.

The study looked at the inflammation using different approaches, where it looked at the expression of adhesion molecules on the proinflammatory monocytes as well as it analysed the expression of the stress proteins Heat-shock proteins (HSPA1A and HSPB1)on the PBMCs.

Detailed description: This is a double-blind randomized control trial with parallel design, where consented overweight and obese women from Chester city in the UK will be randomly assigned into two groups one group CLA will receive 4.5 g/day CLA mixture capsules while the other group will receive a placebo.

Participants will attend three clinics and by the end of each clinic, the participants will be asked to provide 20 ml venous blood samples for the analysis of the biological marker. Participants' anthropometric, body composition, lung functions, Leptin adiponectin, lipid profile, Adhesion molecules CD14, CD16, CD11b, and CD62L, HSPA1A, and HSPB1 will be assessed at three time points, at baseline after 6 and 12 weeks. The level of CLA in the plasma, as well as lipid profile (HDL, LDL, TC, TG), will be measured at each time point

Participants will be asked to fill three food diaries before attending each clinic. Body composition will be measured using bioelectric impedance, lung functions will be assessed using spirometers, adiponectin and leptin will be assessed using ELISA, and finally, CD11b, CD62L, HSPA1A, and HSPB1 will be analysed using flow cytometer. Plasma level of c9, t11-CLA and t10, c12-CLA will be measured using flame ionized Gas chromatography, and the lipid profile will be assessed using ALERE AFINION™ AS100 ANALYZER.

Power calculation for the RCT Sample size calculation is done using G\*Power software, a total of 20 participant is required, 10 participants in each group, to get an effect size of 1.3 kg/m2 change in BMI from baseline and SD of 0.45, 0.05 margin of error, 95% power and 95% confidence interval. Considering a 150% drop out the total number will be 50, 25 in each group.

Participants' randomisation will be performed by an independent third party who is not involved in the current trial. Participants will be randomised into blocks using (www.randomization.com) which generate the randomisation plan. All the capsules will be packed in a light protective dark brown tamper-proof container. The randomised participants will be either allocated to the CLA group or the placebo group. CLA and placebo capsules will have the same shape and colour, and both the participants and researcher will be blind to the treatments.

Statistical analysis. IBM SPSS Statistic Data Editor Software (version25) will be used for the statistical analysis of this trial while the graphs will be made using GraphPad Prism version 7.

Descriptive statistics of baseline continuous data will be expressed in form of mean± standard error of the mean (SEM). Nominal data will be expressed in percentages. The parametric assumption will be checked using Shapiro-Wilk tests at a significant level p\< 0.05. The differences between the baseline characteristics in CLA and the placebo group will be done using an independent t-test in parametric data or Mann Whitney U for non-parametric data, at a significant level P\<0.05.

Testing the effects of CLA compared to placebo and the interaction with times (baseline, 6 weeks, and 12 weeks) will be done using Mixed Model Repeated Measures Analysis of Variance (ANOVA) at a significant level p\< 0.05. The later analysis will be useing Tukey post hoc test with Bonferroni correction for all the measured parameters.

A paired t-test or Wilcoxon test will be done to detect the difference within- participants at different time points in parametric and non-parametric data, respectively, at a significant level P\<0.05. Independent t-test or Mann Whitney U will be used to detect the difference between the CLA group and placebo across the different time points for normally and non-normally distributed data, respectively at a significant level P\<0.05.

The difference in the change at week 6 compared to baseline, (∆ 6 weeks), and at week 12 compared to baseline (∆ 12 weeks), in CLA groups compared to placebo will be checked using t-test in case of normally distributed data or Mann Whitney-U for non-parametric data at significant level P\<0.05. The difference between the categorical data will be done using the Chi-square test at a significant level p\<0.05.

Obesity hypotheses

H1: There is a significant reduction in BMI in CLA supplemented group compared to the placebo group.

H0: There is no significant reduction in BMI in CLA supplemented group compared to the placebo group.

H2: There is a significant reduction in BW in the CLA supplemented group compared to the placebo group.

H0: There is no significant reduction in BW in the CLA supplemented group compared to the placebo group.

H3: There is a significant reduction in WHR in CLA supplemented group compared to the placebo group.

H0: There is no significant reduction in WHR in CLA supplemented group compared to the placebo group.

H5: There is a significant increase in LBM in CLA supplemented group compared to the placebo group.

H0: There is no significant increase in LBM in CLA supplemented group compared to the placebo group.

H6: There is a significant increase in %LBM in CLA supplemented group compared to the placebo group.

H0: There is no significant increase in %LBM in CLA supplemented group compared to the placebo group.

H8: There is a significant reduction in TBF in CLA supplemented group compared to the placebo group.

H0: There is no significant reduction in TBF in CLA supplemented group compared to the placebo group.

H9: There is a significant reduction in %BF in CLA supplemented group compared to the placebo group.

H0: There is no significant reduction in %BF in CLA supplemented group compared to the placebo group.

H10: There is a significant increase in the basal metabolic rate in the CLA supplemented group compared to the placebo group.

H0: There is no significant increase in the basal metabolic rate in the CLA supplemented group compared to the placebo group.

Lung function hypotheses Primary hypothesis H1: There is a significant increase in %PEF predicted in CLA supplemented group compared to the placebo group.

H0: There is no significant increase in %PEF predicted in CLA supplemented group compared to the placebo group.

Secondary hypotheses. H2: There is a significant increase in %FEV1 predicted in CLA supplemented group compared to the placebo group.

H0: There is no significant increase in %FEV1 predicted in CLA supplemented group compared to the placebo group.

H3: There is a significant increase in %FVC predicted in CLA supplemented group compared to the placebo group.

H0: There is no significant increase in %FVC predicted in CLA supplemented group compared to the placebo group.

H8: There is a significant increase in %FEV1/FVC predicted in CLA supplemented group compared to the placebo group.

H0: There is no significant increase in %FEV1/ FVC predicted in CLA supplemented group compared to the placebo group.

8.6.3 Adipokines hypotheses Primary hypothesis H1: There is a significant reduction in leptin in the CLA supplemented group compared to the placebo group.

H0: There is no significant reduction in leptin in the CLA supplemented group compared to the placebo group.

Secondary hypothesis. H2: There is a significant increase in adiponectin in the CLA supplemented group compared to the placebo group.

H0: There is no significant increase in adiponectin in the CLA supplemented group compared to the placebo group.

8.6.4 Inflammation hypotheses Primary hypothesis H1: there is a significant change in the expression of HSPA1A on PBMCs in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of HSPA1A on PBMCs in the CLA group compared to the placebo group.

Secondary hypotheses H2: there is a significant change in the expression of HSPA1A on lymphocytes in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of HSPA1A on lymphocytes in the CLA group compared to the placebo group.

H3: there is a significant change in the expression of HSPA1A on monocytes in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of HSPA1A on monocytes in the CLA group compared to the placebo group.

H4: there is a significant change in the expression of HSPB1on PBMCs in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of HSPB1 on PBMCs in the CLA group compared to the placebo group.

H5: there is a significant change in the expression of HSPB1 on lymphocytes in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of HSPB1 on lymphocytes in the CLA group compared to the placebo group.

H6: there is a significant change in the expression of HSPB1 on monocytes in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of HSPB1 on monocytes in the CLA group compared to the placebo group.

H7: there is a significant change in the expression of CD11b on pro-inflammatory monocytes (CD14++CD16+) in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of CD11b on pro-inflammatory monocytes (CD14++CD16+) in the CLA group compared to the placebo group.

H8: there is a significant change in the expression of CD11b on pro-inflammatory monocytes (CD14++CD16+) after 100ng/ml LPS stimulation for one hour in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of CD11b on pro-inflammatory monocytes (CD14++CD16+) in the CLA group compared to the placebo group.

H9: there is a significant change in the increase of CD11b expression on pro-inflammatory monocytes (CD14++CD16+) after LPS stimulation in the CLA group compared to the placebo group.

H0: there is no significant difference H8: there is a significant change in the increase of CD11b expression on pro-inflammatory monocytes (CD14++CD16+) after LPS stimulation in the CLA group compared to the placebo group.

H10: there is a significant change in the expression of CD62L on pro-inflammatory monocytes (CD14++CD16+) in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of CD62L CD11b on pro-inflammatory monocytes (CD14++CD16+) in the CLA group compared to the placebo group.

H11: there is a significant change in the expression of CD62L on pro-inflammatory monocytes (CD14++CD16+) after 100ng/ml LPS stimulation for one hour in the CLA group compared to the placebo group.

H0: there is no significant change in the expression of CD62L on pro-inflammatory monocytes (CD14++CD16+) in the CLA group compared to the placebo group.

H12: there is a significant change in the reduction of CD62L expression on pro-inflammatory monocytes (CD14++CD16+) after LPS stimulation in the CLA group compared to the placebo group.

H0: there is no significant change in the reduction of CD62L expression on pro-inflammatory monocytes (CD14++CD16+) after LPS stimulation in the CLA group compared to the placebo group.

Lipid profile hypotheses H1: there is a significant change in the level of LDL in the CLA group compared to the placebo group.

H0: there is no significant change in the level of LDL in the CLA group compared to the placebo group.

H2: there is a significant change in the level of HDL in the CLA group compared to the placebo group.

H0: there is no significant change in the level of HDL in the CLA group compared to the placebo group.

H3: there is a significant change in the level of TC in the CLA group compared to the placebo group.

H0: there is no significant change in the level of TC in the CLA group compared to the placebo group.

H4: there is a significant change in the level of TG in the CLA group compared to the placebo group.

H0: there is no significant change in the level of TG in the CLA group compared to the placebo group.

Eligibility criteria: Inclusion Criteria:

* Able to swallow capsules
* Overweight and obese women (BMI≥25)
* Forced expiratory volume FEV1≥ 70%

Exclusion Criteria:

* Participants taking antibiotics,
* Participants taking weight loss medications
* Pregnant and breastfeeding women,
* Women with current or a history of severe lung disease

Primary outcomes:
measure: The change in body weight from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
measure: The change in BMI from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
measure: The change in total body fat from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
measure: The change in percentage body fat from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
measure: The change in Lean body mass from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
measure: The change in percentage lean body mass from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
measure: The change in waist circumference from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
measure: The change in waist to hip ratio from baseline to 12 weeks
timeFrame: 0, 6, 12 Weeks
Secondary outcomes:
measure: The change in Total Cholesterol (TC) from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in Triglycerides (TG) from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in Low Density Lipoprotein (LDL) from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in (High Density Lipoprotein) HDL from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
Other outcomes:
measure: The change in (Forced Expiratory Volume) FEV% predicted from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in (Forced Vital Capacity) FVC% predicted from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in (Peak of Flow) PEF% predicted from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in expression of CD11b on pro-inflammatory monocytes (CD14++CD16+) from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in expression of CD62L on pro-inflammatory monocytes (CD14++CD16+) from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in the plasma level of Leptin from baseline to 12 weeks
timeFrame: 0,6,12 weeks
measure: The change in the plasma level of Adiponectin from baseline to 12 weeks
timeFrame: 0,6,12 weeks
measure: The change in expression of HSPA1A on PBMCs from baseline to 12 weeks
timeFrame: 0, 6, 12weeks
measure: The change in expression of HSPB1 on PBMCs from baseline to 12 weeks
timeFrame: 0, 6, 12weeks
measure: The change in plasma level of c9,t10-CLA from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
measure: The change in plasma level of t10, c12-CLA from baseline to 12 weeks
timeFrame: 0, 6, 12 weeks
Locations:
city: Chester
country: United Kingdom
facility: University of Chester
state: Cheshire
Study officials:
affiliation: University of Chester
name: Hanady Hamdallah, PhD
role: PRINCIPAL_INVESTIGATOR
References: