Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04647175 |
| Other study ID # |
1-10-72-102-19 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 23, 2020 |
| Est. completion date |
June 1, 2022 |
Study information
| Verified date |
March 2022 |
| Source |
University of Aarhus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In a triple-crossover study, the effect aronia consumption on type 2 diabetes will be
examined. 48 type 2 diabetes patients need to complete the trial. Each patient will receive
two daily doses of both fermented aronia, aronia, or placebo for eight weeks each. There will
be 3 weeks wash-out periods between the intervention periods. Before and after the
intervention periods, various measurements will be performed to assess the effects of aronia,
fermented aronia, and placebo on type 2 diabetes.
Description:
Hypothesis: Fermented aronia extract (FAE) improves glycaemia and lipidaemia in T2D more
efficiently than both non-fermented aronia extract (NFAE) and placebo.
Research questions:
Does FAE/NFAE when administered to T2D subjects:
- Improve glucose responses to an oral glucose tolerance test and HbA1C?
- Improve fasting LDL-, HDL- and total cholesterol?
- Reduce insulin resistance and increase total antioxidative/anti-inflammatory capacity?
- Increase circulating GLP-1 and GIP levels with lower DPP4 activity?
- Alleviate hypertension and obesity?
Methods A total of 48 T2D patients is needed for the double blind, randomized triple
cross-over trial. The patients will consume FAE, NFAE or placebo daily divided into two doses
which is expected to provide a sufficient dose of bioactive phenolic compounds. The patients
will be recruited through "forsoegsperson.dk", "sundhed.dk", and flyers placed at Aarhus
university hospital (AUH). T2D patients with fasting blood glucose ≤ 12 mM and HbA1c > 6.1%
and < 10%, without severe comorbidities, will be included. Before enrolment, the patients
receive all necessary study information (written and oral) including potential adverse
effects (e.g. aronia allergy), and they will have to provide their informed consent (visit
1). There will be an assessment of whether the patients fulfill the criteria as well.
The randomized double-blinded triple cross-over study consists of three eight weeks
intervention periods (placebo, FAE and NFAE), where the participants are randomly assigned to
the order of treatments (six different possibilities of order). The intervention periods are
separated by minimum three weeks wash-out periods (see figure 1 for details). Before and
after each intervention period, i.e. six times, oral glucose tolerance tests (OGTT) will be
performed. The Central Denmark Region Committees on Health Research Ethics has approved the
trial.
Analyses OGTT: Prior to the OGTT, the participants have fasted for 8 hours where after they
will consume 75 g glucose dissolved in 300 ml water within 5 minutes. Blood will be sampled
at time points -10, 0, 30, 60, 90, 120, and 240 minutes.
Blood Analyses: After the blood sampling, plasma will be stored at -80° C until further
analysis. Obviously, the investigators aim to determine if FAE and NFAE consumption is
capable of lowering the fasting and postprandial blood sugar and thus, the levels of glucose,
fructosamin and HbA1c will be measured. The concentration of advanced glycosylation end
products will be assessed in fasted blood samples. Also, lipidaemia will be examined, e.g.
total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein
concentrations. The inflammatory state will be assessed by measuring the level of pro- and
anti-inflammatory cytokines as well as the concentration of C-reactive protein in fasting
blood samples. To determine whether aronia acts through incretin mediated regulation, the
concentrations of GIP and GLP-1 and the activity of DDP4 will be measured. The concentrations
of glucagon, insulin, and adiponectin will be assessed as well.
Insulin resistance: β-cell dysfunction and insulin resistance will be estimated from blood
glucose and insulin concentrations using Homeostasis Model Assessment (3) and Matsuda Index
(4) which are based on concentrations measured at fasting states and during the OGTT,
respectively.
Diurnal blood pressure: 24-hour ambulatory blood pressure monitoring will be carried out. The
necessary equipment is available at AUH. The participants will have their 24-hour blood
pressure measured before and after each intervention period.
Body mass index (BMI): At the first visit the participants height and weight are measured,
and the weight will subsequently be monitored.
Metabolomics and microbiomics assays: The results from the previous tests (effects on main
outcomes) will determine the extent of the subsequent metabolomics and microbiomics analyses.
Fecal samples for microbiomics, as well as blood and urine samples for metabolomics will be
stored at -80° C until use.
Data analysis: The power calculation is based on our primary effect parameter glucose
incremental area under the curve (iAUC). The number of participants needed to obtain a
statistical power of 80% at a level of P<0.05 (α=0.05; 1-β=0.8) was calculated as 48. The
investigators wanted to detect a minimal relevant difference for the area of (mean ± s.d.)
65±50 mmol/l x 120 min, which gives us an estimated effect size of 1.30. The anticipated
dropout is 20%. ANOVA will be conducted for each variable to determine if the variables
change upon administration of FAE, NFAE, or placebo as well as to assess intergroup
variability at baseline and endpoint. Significance will be set to p < 0.05.
