Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06067113 |
| Other study ID # |
PIC044-23_HRJC |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 15, 2023 |
| Est. completion date |
February 28, 2024 |
Study information
| Verified date |
June 2023 |
| Source |
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz |
| Contact |
Jose Fernandez-Ferro, MD MSc |
| Phone |
659136245 |
| Email |
jose.fferro[@]hospitalreyjuancarlos.es |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This prospective study is intended to explore differences in the cerebral hemodynamics and
vascular functional characteristics between obese and normo-constituted patients; as well as
the changes in the hemodynamic and functional characteristics in those same obese patients
following the intense weight-loss that happens after bariatric surgery.
Description:
Obesity, defined by the World Health Organization (WHO) as a body mass index of 30 or higher,
is reaching epidemic proportions worldwide, with some 2.8 million attributable deaths
annually. Initially linked to countries with higher incomes, it is now a serious health
problem in countries with medium and low incomes.
The increase in body mass index from overweight to obesity is linearly correlated with an
increase in coronary and cerebral vascular events, as well as death from vascular causes.
Apart from the fact that obese patients are at higher risk of having classic vascular risk
factors (independently associated with atherosclerosis and a risk of vascular events), the
evident linear relationship between obesity and vascular pathology suggests the existence of
pathophysiological mechanisms related to the accumulation of fat that cause structural and
functional damage to the vascular system.
Adipokines are a group of pro-inflammatory peptides specifically secreted by fat tissue that
have been linked to inflammatory activity, endothelial dysfunction, and insulin resistance in
overweight and obese conditions. From these studies, a wealth of knowledge is drawn on the
relationship of obesity with large-vessel atherosclerosis; but yet, few studies have focused
on the particular relationship of obesity on the cerebral vasculature, despite the strong
epidemiological relationship between obesity in middle age (and vascular risk factors in
general) and cognitive deficits and vascular dementia in the elderly, possibly driven to a
large extent by cerebral small vessel disease.
Small vessel disease (including both radiological signs on MRI in the form of white matter
lesions, lacunar infarcts and/or cognitive impairment, and vascular dementia/Alzheimer's
disease) have been positively correlated in several retrospective and prospective studies
with the Gosling index or pulsatility index (PI) obtained by transcranial Doppler study in
the middle cerebral artery. In recent years, much importance has been attached to the
potential deleterious impact that small cerebral vessel disease in middle ages may have on
degenerative brain diseases over 60 years of age, however, we have not identified a specific
study of haemodynamic factors of cerebral circulation in middle-aged patients.
Obese patients with an indication for bariatric surgery constituted, in our opinion, an
excellent model for the study of these potential haemodynamic factors (surrogate markers of
subclinical cerebrovascular disease) in two ways: by comparing them with normal-constituted
volunteers; as well as comparing them with themselves once they achieve an effective
reduction in their body weight after surgery.
PRIMARY OBJECTIVE
To compare hemodynamic parameters of the cerebral circulation (mean arterial velocity and
pulsatility index in the middle cerebral artery) of a sample of obese patients elective for
bariatric surgery, in two ways: 1) with a sample of matched normal-weight volunteers by sex
and age; 2) with themselves once they have achieved a loss of at least 25% of their original
weight after surgery.
SECONDARY OBJECTIVES
To compare the following hemodynamic and functional indices between obese patients and
normal-constituted volunteers, as well as between obese patients before and after losing at
least 25% of their original weight after surgery:
DESCRIPTION OF THE INTERVENTION:
1. BASELINE VISIT
The first visit (baseline visit) is similar for both patients and normal weight
volunteers. It is divided into three parts:
FIRST: interview with the patient to collect epidemiological and anthropometric data,
including age, sex, height, weight, BMI, classic vascular risk factors, abdominal
perimeter and drugs being taken.
SECOND: the patient is instructed to lie down on the stretcher in a quiet environment
with soft light in the room. After about 5 minutes of rest, blood pressure will be taken
in the arms and legs for the subsequent calculation of the ankle-brachial index. Next,
the endothelium-dependent vasodilation protocol will be carried out as follows: 1)
initial measurement of the longitudinal diameter of the maximum brachial artery in
systole from a frozen duplex image, in the middle third of one of the two arms
(indistinctly); 2) a blood pressure cuff is placed on the same arm, which is inflated
above 200 mm Hg (ensuring with a stethoscope that there is no tapping of the arterial
pulse, or in other words, that effective ischemia occurs ). 3) Ischemia is maintained
for 4 minutes using a stopwatch. 4) When the 4 minutes are up, the cuff is deflated and
an attempt is immediately made to re-locate the brachial artery in a longitudinal
section during the first minute releasing off the cuff; 5) one minute after deflating
the cuff, with the artery already located, a measurement of the maximum diameter of the
brachial artery in systole is taken again from a frozen image.
THIRD PART: this last part consists of 4 parts:
(A) Ultrasound study of supra-aortic trunks: IMT, mean arterial velocity and IP in
terminal ACC and first segment of the cervical ICA after bifurcation.
(B) Cannulation of a peripheral venous line. (C) Reconstitution of SONOVUE® contrast and
administration of half the ampoule (the second half ampoule will be administered only in
case all the desired measurements cannot be performed.
(D) Transcranial duplex study with contrast, adjusting the power to acquire the
following serial measurements:
D.1 Peak-systolic, diastolic and mean arterial velocity in terminal ICA, middle segment
of MCA, PCA-P1, ACA-A1 through transtemporal window of the most favorable side.
Pulsatility index in the same arterial segments
D2. Peak-systolic, diastolic and mean arterial velocity in the middle third of the
basilar artery (BA) through transforaminal window. Pulsatility index in this segment.
2. FOLLOW-UP VISIT (PATIENTS ONLY)
FIRST: interview with the patient to collect: weight, BMI, classic vascular risk
factors, abdominal perimeter and drugs being taken.
SECOND: the patient is instructed to lie down on the stretcher in a quiet environment
with little light in the room. After a rest of about 5 minutes, blood pressure will be
taken in the arms and legs for the subsequent calculation of the ankle-brachial index.
Next, the endothelium-dependent vasodilation protocol will be carried out as follows: 1)
initial measurement of the longitudinal diameter of the maximum brachial artery in
systole from a frozen duplex image, in the middle third of one of the two arms (
indistinctly); 2) a blood pressure cuff is placed on the same arm, which is inflated
above 200 mm Hg (ensuring with a stethoscope that there is no tapping of the arterial
pulse, or in other words, that effective ischemia occurs ). 3) Ischemia is maintained
for 4 minutes using a stopwatch. 4) When the 4 minutes are up, the cuff is deflated and
an attempt is immediately made to re-locate the brachial artery in a longitudinal
section during the first minute after deflating the cuff; 5) one minute after deflating
the cuff, with the artery already located, a measurement of the maximum diameter of the
brachial artery in systole is taken again from a frozen image.
THIRD PART: this last part consists of 3 parts:
(A) Ultrasound study of supra-aortic trunks: IMT, mean arterial velocity and IP in
terminal ACC and first segment of the cervical ICA after bifurcation.
(B) Cannulation of a peripheral venous line. (C) Reconstitution of the SONOVUE® contrast
and administration of half the ampoule (the second half ampoule will be administered
only in case all the desired measurements cannot be performed.
(D) Transcranial duplex study with contrast, adjusting the power to acquire the
following serial measurements:
D.1 Peak-systolic, diastolic and mean arterial velocity in terminal ICA (ICA-T), middle
segment of MCA, PCA-P1, ACA-A1 through transtemporal window of the most favorable side.
Pulsatility index in the same arterial segments.
D2. Peak-systolic, diastolic and mean arterial velocity in the middle third of the
basilar artery (BA) through transforaminal window. Pulsatility index in this segment.
DEVELOPMENT OF THE STUDY AND EVALUATION OF THE RESPONSE
Recruitment will be carried out from the general surgery consultation, when it is
decided to include the patient on the surgical waiting list, once the previous
evaluation study has been completed and their suitability has been confirmed. At that
time the possibility of participating in the study is explained to them. If the patient
is interested, the general surgeon informs one of the study neurologists of this
interest, who will contact him/her by telephone to offer further explanations about the
type of study and possible discomfort caused orally, in addition to sending the informed
consent via email. so you can read it calmly. If the patient decides to participate, she
will communicate via email in response to the neurologist's initial sending with the
signed and scanned informed consent, which will be saved in electronic format.
Next, a day/time is agreed with the patient to carry out the initial visit. On that day,
the patient will provide the signed informed consent in paper format, which will also be
kept.
Taking into account the sex and age characteristics of each of the patients, volunteers
matched by age and sex with BMI below 25 will be recruited, recruited from the general
neurology clinic or from non-blood relatives of the recruited patients. . In number of
at least 10. The procedure and the tests to be performed will be the same as in the case
of patients.
GENERAL SCHEME
VISIT 0 Patient Selection in General Cx consultations. Permission for telephone contact.
VISIT 1 Telephone call to explain the study process and sending of informed consent by
email, which must be signed and scanned and brought in person
VISIT 2 Baseline Visit:
- Clinical interview
- Functional indices
- Ultrasound study
VISIT 3 Follow-up visit (applicable only to patients, at least 12 months after surgery
and if they have lost at least 25% compared to initial weight):
- Clinical interview
- Functional indices
- Ultrasound study
EVALUATION OF RESULTS
Primary Analysis
Comparison of epidemiological variables, VAM, PI and functional indices (ankle-brachial
index and endothelium-dependent vasodilation) between the group of obese patients before
surgery and a group of normal weight volunteers, matched by sex and age. This will be
done through a statistical analysis in three steps:
- Descriptive analysis of both populations using measures of central tendency
(proportions or standard deviations)
- Univariate analysis using non-parametric tests
- Logistic regression where the factors most related to obese patients or those
clinically relevant are included, even if they do not meet the defined statistical
criterion.
Secondary analyzes
Comparison of epidemiological variables, VAM, PI and functional indices between the
group of obese patients before surgery and the same group at least 12 months after
surgery and once they have lost at least 25% of their original weight. This will be done
through a statistical analysis in three steps:
- Descriptive analysis of both populations using measures of central tendency
(proportions or standard deviations)
- Univariate analysis using non-parametric tests
- Logistic regression where the factors most related to obese patients or those
clinically relevant are included, even if they do not meet the defined statistical
criterion.
ADVERSE EVENTS
This is an observational study without active intervention. The only potential risks are
described below and are not considered slight or minor in all cases:
- The derivatives of the canalization of a peripheral venous access can be pain and
hemorrhages, in both cases located in the puncture area and temporary.
- The risks derived from the administration of eco-enhancers are mild and temporary.
Nausea, vomiting, headaches, altered taste, dizziness and skin rashes have been
reported. Serious adverse reactions such as hypotension, bronchospasm and urticaria
have been described in 0.001-0.006% of patients.
- The risks associated with performing the endothelium-dependent vasodilation study
due to controlled ischemia in one arm are local pain and ecchymosis, both
temporary.
No adverse effects have been described after performing cervical or transcranial
ultrasound.
ETHICAL ASPECTS
GENERAL AND SPECIFIC RULES FOR RESEARCHERS
The researchers will strictly adhere to the provisions of this protocol, properly
completing the data collection notebooks. The study will be carried out in accordance
with the recommendations contained in the Declaration of Helsinki, revised at successive
world assemblies (last in Fortaleza, Brazil, October 2013) and the Standards of Good
Clinical Practice.
The research team (recruitment, explanation and procedures with patients, anonymization)
is made up of members of the General Surgery and Endocrinology and Nutrition services,
in addition to Dr. Álvaro Bonelli Franco of Neurology. The data analyzes will be
performed blindly by Drs. Teresa Montalvo and Jose Fdez. Ferro from the Neurology
service.
INFORMED CONSENT All patients will be informed before starting the study of the
objectives and procedures that will be carried out. The patient information sheet and
informed consent models appear in Annex 1 and 2 of this protocol.
SECURITY AND CONFIDENTIALITY DEVICES The information disseminated and obtained by the
implementation of this study is considered confidential and will be treated at all times
in accordance with Organic Law 3/2018, of December 5, on the Protection of Personal Data
and guarantee of digital rights and in Regulation (EU) 2016/679 of the European
Parliament and of the Council of 04/27/2016. An Excel database will be created
specifically designed for the study, in which patients will be identified with a
numerical code assigned in order of recruitment, and which will not contain personal
information about the patients.
SURE The only interventions that the patient will be subjected to during the study are
venipuncture, the infusion of potentiators and the performance of a transient ischemia
in one arm, all of them considered very low-cost interventions, therefore, they are not
considered It is necessary to take out civil liability insurance.
ECONOMIC MEMORY
This study arises from an independent initiative of the researchers. No type of
financial remuneration is contemplated either for the patient or for the study
researchers. To cover the expenses derived from the use of eco-enhancers (Sonovue®) as
well as the costs of writing and translating the manuscript for a potential competitive
publication of the results, the project will be submitted to research aid competitions
where appropriate.
PRACTICAL CONSIDERATIONS
Researchers will adhere to the standards of Good Clinical Practice. All information
collected during the study will be recorded directly in the attached data collection
notebook. When a correction is made, the date and initials of the person making it must
be noted. Prior to the study, the patient must receive oral and written information
regarding the design, purposes of the study and possible risks that may arise from it.
If they subsequently agree to participate in it, they must sign their consent, without
this preventing them from revoking it at any time and for any reason and abandoning the
study. Patients will be instructed regarding the need to strictly follow the
investigators' instructions. Patients will be informed of the need to contact the
researchers if any incident arises during the study, providing them with how to do so.
There will be an electronic documentation file for all data, which will be kept intact
for ten years after completion of the study.
STATISTIC ANALYSIS
SAMPLE SIZE The absence of previous studies makes it difficult to calculate the sample
size following a rigorous statistical method. We have thought about including 15
patients with obesity, estimating a 20% loss during follow-up for various reasons
(revocation of their participation during follow-up or not achieving the minimum weight
loss estimated a priori despite the surgery, which we set in 25%). We believe that the
differences between patients and healthy controls, as well as between patients before
and after losing weight, will be considerable in both hemodynamic and functional factors
to observe differences with this number of participants, in view of the published
observational studies. previously.
STATISTIC ANALYSIS It will be carried out with the appropriate statistical techniques
for the prespecified study variables. A descriptive analysis of the population is
carried out. Frequency results will be expressed in absolute terms, as percentages and
confidence intervals. Continuous variables will be expressed as mean (SD) and median
(range) according to the normality test (Kolmogorov Smirnov test). To study the
relationship between the different variables, Chi square or Analysis of Variance will be
used if they are parametric. And if a normal distribution is not followed, a
non-parametric test will be used (Mann-Whitney U or Kruskal Wallis, as appropriate). The
SPSS 18 statistical package (SPSS Inc. Chicago, IL, USA) will be used.
