Endothelial DysfunctionNCT03053986
Effect of Apple Polyphenols on Vascular Oxidative Stress and Endothelium Function Study (APP trial_2016)
A study testing Apple polyphenols in people with Endothelial Dysfunction, run by University of Bologna at 1 site in Italy.
Trial summary
Apple polyphenols are mostly acknowledged for their hypoglycaemic properties, but represent an apple active fraction with many pharmacological functions. The study aim was to examine their effect on uricemia and endothelial function in a sample of overweight subjects. This was a two-phases study. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Endothelial Dysfunction
- What is being tested?
- Apple polyphenols
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteItaly
- Study dates
- 1 Sep 2016to 1 Jun 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index (BMI)>25 kg/m2
- Fasting plasma glucose 100 mg/dL ≤ FPG ≤ 125 mg/dL
Who cannot join
- Patients with obesity (body mass index [BMI] <30 Kg/m2)
- diabetes mellitus
- personal history of atherosclerosis-related cardiovascular diseases (coronary artery disease
- cerebrovascular disease
- ultrasound diagnosed carotid atherosclerosis)
- absorption disease
Show all 9Show fewer
- myopathy
- renal failure or chronic liver disease
- serious or invalidating other diseases reducing the subjects' ability to comply with the full protocol were excluded from the study as well as subjects with a known apple intolerance.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-blind, Placebo-controlled, Randomized Clinical Trial on the Metabolic and Vascular Effects of a Dietary Supplementation With Apple Polyphenols in Overweight Subjects
Apple polyphenols are mostly acknowledged for their hypoglycaemic properties, but represent an apple active fraction with many pharmacological functions. The study aim was to examine their effect on uricemia and endothelial function in a sample of overweight subjects. This was a two-phases study. The in vitro experiment aimed to evaluate the apple polyphenols' ability to lower uric acid in comparison with allopurinol. The in vivo study consisted in a randomized, double-blind, parallel placebo-controlled clinical trial involving 62 overweight volunteers with suboptimal values of fasting plasma glucose (100 mg/dL≤FPG≤125 mg/dL), randomized to be treated with 300 mg apple polyphenols or placebo for 8 weeks.
Read the detailed description
The study included a 2-week run-in period of diet standardization and an 8-week treatment period. At enrolment, patients were given standard behavioural and qualitative dietary suggestions to correct their unhealthy habits. In particular, subjects were strongly recommended to follow the general indications of a Mediterranean diet, avoiding an excessive intake of diary and red meat derived products and reducing the dietary excesses, in order to maintain an overall balanced diet for the entire duration of the study. Individuals were also encouraged to increase their physical activity by walking briskly or cycling from 3 to 5 times for week, at least 20 minutes every time.
The study fully complied with the ethical guidelines of the Declaration of Helsinki. The study protocol was approved by the Ethical Committee of the University of Bologna. All patients signed a written informed consent to participate.
After 2 weeks of diet standardization, the enrolled subjects were allocated to the treatment with an indistinguishable pill of placebo or an active product, containing 300 mg of apple extract (Malus Domestica) with glycosilated polyphenols (≥90%) including glycosilated phloritzin (15-30%), chlorogenic acid (10-25%) and quercetin (15-25%) (kindly provided by Amitalia Srl, Solara, MI, Italy). Patients were asked to take the pills regularly, every day early in the morning. The amount of glycosilated polyphenols was assessed spectophotometrically at 280 nm, using synthetic catechin as standard. Glycosilated phloritzin, chlorogenic acid and quercetin were measured by HPCL-MS [high performance liquid chromatography-mass spectrometry].
The randomization was performed 1:1 ratio and the blocks were stratified by sex and age. An alphabetical code was assigned to each lot code (corresponding to treatment or placebo) impressed on the dose box. The study staffs and the investigators, as well as all of the volunteers, were blinded to the group assignment. Codes were kept in a sealed envelope, which was not opened until the end of the trial. Dose boxes were mixed and a blinded dose box was assigned to each enrolled patient.
Patients were evaluated anamnestically and by the execution of a physical examination and laboratory analyses at the baseline, in the middle and at the end of the trial.
The hemodynamic variables recorded (endothelial function, arterial stiffness and related parameters) were investigated before and after the intervention period. All the instrumental measurements were carried out following standardized protocols by specially trained staff.
- Conditions
- Endothelial Dysfunction
- Being tested
- Apple polyphenols, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apple polyphenolsDietary supplement
1 tablet per day at evening before sleeping
PlaceboOther
1 tablet per day at evening before sleeping
| Study group | Role | What they receive |
|---|---|---|
| Apple polyphenols | Active comparator | White capsule containing 300 mg of apple extract (Malus Domestica) with glycosilated polyphenols (≥90%) including glycosilated phloritzin (15-30%), chlorogenic acid (10-25%) and quercetin (15-25%) Receives: Dietary Supplement: Apple polyphenols |
| Placebo | Placebo comparator | Indistinguishable capsules with similar dimension, colour, odour and taste Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial function
Change in arterial diameter after ischemic stimulus
Measured: 8 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study start1 Sep 2016
- Primary completion1 Jun 2017
- Study completion1 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Endothelial DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bologna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Claudio Borghi, University of Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03053986
- Sponsor's protocol ID
- APP trial_2016
- Status last verified
- Jan 2024
- First submitted
- 7 Feb 2017
- Last updated
- 1 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Cicero AFG, Caliceti C, Fogacci F, Giovannini M, Calabria D, Colletti A, Veronesi M, Roda A, Borghi C. Effect of apple polyphenols on vascular oxidative stress and endothelium function: a translational study. Mol Nutr Food Res. 2017 Nov;61(11). doi: 10.1002/mnfr.201700373. Epub 2017 Sep 1.
PubMed 28755406
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Placebo-controlled, Randomized Clinical Trial on the Metabolic and Vascular Effects of a Dietary Supplementation With Apple Polyphenols in Overweight Subjects
- ClinicalTrials.gov ID
- NCT03053986
- Acronym / sponsor ID
- APP trial_2016
- Conditions
- Endothelial Dysfunction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of BolognaUniversity, hospital or other
- Study start
- 1 Sep 2016 (actual)
- Primary completion
- 1 Jun 2017 (actual)
- Study completion
- 1 Jun 2017 (actual)
- First posted
- 15 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Apple polyphenols are mostly acknowledged for their hypoglycaemic properties, but represent an apple active fraction with many pharmacological functions. The study aim was to examine their effect on uricemia and endothelial function in a sample of overweight subjects. This was a two-phases study. The in vitro experiment aimed to evaluate the apple polyphenols' ability to lower uric acid in comparison with allopurinol. The in vivo study consisted in a randomized, double-blind, parallel placebo-controlled clinical trial involving 62 overweight volunteers with suboptimal values of fasting plasma glucose (100 mg/dL≤FPG≤125 mg/dL), randomized to be treated with 300 mg apple polyphenols or placebo for 8 weeks.
Detailed description
The study included a 2-week run-in period of diet standardization and an 8-week treatment period. At enrolment, patients were given standard behavioural and qualitative dietary suggestions to correct their unhealthy habits. In particular, subjects were strongly recommended to follow the general indications of a Mediterranean diet, avoiding an excessive intake of diary and red meat derived products and reducing the dietary excesses, in order to maintain an overall balanced diet for the entire duration of the study. Individuals were also encouraged to increase their physical activity by walking briskly or cycling from 3 to 5 times for week, at least 20 minutes every time.
The study fully complied with the ethical guidelines of the Declaration of Helsinki. The study protocol was approved by the Ethical Committee of the University of Bologna. All patients signed a written informed consent to participate.
After 2 weeks of diet standardization, the enrolled subjects were allocated to the treatment with an indistinguishable pill of placebo or an active product, containing 300 mg of apple extract (Malus Domestica) with glycosilated polyphenols (≥90%) including glycosilated phloritzin (15-30%), chlorogenic acid (10-25%) and quercetin (15-25%) (kindly provided by Amitalia Srl, Solara, MI, Italy). Patients were asked to take the pills regularly, every day early in the morning. The amount of glycosilated polyphenols was assessed spectophotometrically at 280 nm, using synthetic catechin as standard. Glycosilated phloritzin, chlorogenic acid and quercetin were measured by HPCL-MS [high performance liquid chromatography-mass spectrometry].
The randomization was performed 1:1 ratio and the blocks were stratified by sex and age. An alphabetical code was assigned to each lot code (corresponding to treatment or placebo) impressed on the dose box. The study staffs and the investigators, as well as all of the volunteers, were blinded to the group assignment. Codes were kept in a sealed envelope, which was not opened until the end of the trial. Dose boxes were mixed and a blinded dose box was assigned to each enrolled patient.
Patients were evaluated anamnestically and by the execution of a physical examination and laboratory analyses at the baseline, in the middle and at the end of the trial.
The hemodynamic variables recorded (endothelial function, arterial stiffness and related parameters) were investigated before and after the intervention period. All the instrumental measurements were carried out following standardized protocols by specially trained staff.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apple polyphenols | Active comparator | Dietary Supplement: Apple polyphenolsWhite capsule containing 300 mg of apple extract (Malus Domestica) with glycosilated polyphenols (≥90%) including glycosilated phloritzin (15-30%), chlorogenic acid (10-25%) and quercetin (15-25%) |
| Placebo | Placebo comparator | Other: PlaceboIndistinguishable capsules with similar dimension, colour, odour and taste |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Body mass index (BMI)>25 kg/m2
- Fasting plasma glucose 100 mg/dL ≤ FPG ≤ 125 mg/dL
Key exclusion criteria (9 listed)
- Patients with obesity (body mass index [BMI] <30 Kg/m2)
- diabetes mellitus
- personal history of atherosclerosis-related cardiovascular diseases (coronary artery disease
- cerebrovascular disease
- ultrasound diagnosed carotid atherosclerosis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Apple polyphenols1 tablet per day at evening before sleeping | Dietary supplement | Apple polyphenols |
| Placebo1 tablet per day at evening before sleeping | Other | Placebo |
Primary outcome
Endothelial function
Time frame: 8 week
Change in arterial diameter after ischemic stimulus
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
- Results publication: PubMed 28755406Cicero AFG, Caliceti C, Fogacci F, Giovannini M, Calabria D, Colletti A, Veronesi M, Roda A, Borghi C. Effect of apple polyphenols on vascular oxidative stress and endothelium function: a translational study. Mol Nutr Food Res. 2017 Nov;61(11). doi: 10.1002/mnfr.201700373. Epub 2017 Sep 1.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Apple polyphenols in people with Endothelial Dysfunction, run by University of Bologna at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelial function (time frame: 8 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03053986, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2024.