Study of the Life Expectancy of Patients With Metabolic Syndrome After Weight Loss:
Condition: Obesity
MeSH terms: Metabolic Syndrome; Weight Loss
Study type: Interventional

Summary: 
      Background and study aims:

      Surgical and non-surgical normalization of body weight with obesity leads to a significant
      improvement in health and regression of metabolic syndrome. But as the reduction in body
      weight with obesity changes the life expectancy remains not clear enough.

      The use of endoscopic staplers does not exclude the emergence of serious complications of
      surgery, for example, including bleeding and leakage in the stapler suture line. Therefore,
      the advantages of using a band in the bariatrics are justified from a security standpoint.

      Currently, the gastric bypass is increasingly performed in the version of the mini gastric
      bypass (MGB). Another name for the procedure: one anastomosis gastric bypass (OAGB). The
      proposal to use for the staple-free (stepleless or steplerless) creation of a pouch
      (band-separated gastric bypass) with use for band a vascular prosthesis is justified, but it
      requires comparison of this method with a stapler variant.

      An important issue is comparing surgical and non-surgical weight loss with obesity and
      metabolic syndrome and comparing life expectancy with confirmation of changes in telomere
      length.

      This study compares loss of weight, changes in other health conditions that the patient may
      have (co-morbidities, such as diabetes), telomere length, quality of life, the number of
      complications and side effects, the degree of complexity of the surgical technique and
      operating costs of a new laparoscopic band-separated mini- gastric bypass (LBSMGB) procedure
      compared with the standard stapler (linear cutter) - separated mini-gastric bypass (LSSMGB).
      Additionally, surgical treatment will be compared with non-surgical treatment (hypocaloric
      diet therapy).

      Who can participate? Obese adult patients with a BMI of between 30 kg/m2 and 50 kg/m2. What
      does the study involve? Participants are randomly allocated to one of three groups. Those in
      the first (A) group undergo the laparoscopic band-separated mini-gastric bypass procedure.
      Those in the second (B) group undergo the linear cutter stapler-separated mini-gastric bypass
      procedure. In three (C) group including standard lifestyle intervention on weight and
      hypocaloric diet therapy.

      All patients are then followed up one month after surgery and again after 6 and, finally, 12
      months after surgery where the changing body mass index, changes in co-morbidities, change
      telomere length and quality of life are assessed.
    

Detailed description: 
      Study hypothesis:

      The increase in life expectancy depends on the degree of weight loss and the degree of
      regression of metabolic syndrome manifestations.

      Ethics approval May 24, 2018, Ethics Committee of the Corporate Fund "University medical
      center".

      Study design:

      The interventional prospective randomized controlled clinical trial single-center study

      Primary study design:

      Interventional.

      Secondary study design:

      Randomised controlled trial.

      Trial setting:

      Hospitals.

      Trial type:

      Treatment.

      Patient information sheet:

      Not available in web format, please use contact details to request a participant information
      sheet.

      Condition:

      Morbid obesity.

      Intervention type:

      Procedure/Surgery

      Background The prevalence of obesity in Kazakhstan in 2017 was more than 20% of the
      population. The annual increase in obesity rates over the past five years was 3.9 percent.
      Metabolic syndrome (MetS), which is based on abdominal adiposity, is a complex of symptoms
      that are risk factors for cardiovascular disease, manifestations of type 2 diabetes or
      prediabetes, non-alcoholic fatty liver disease, and dyslipidemia. Clinical MetS play a
      leading role in reducing the life expectancy and mortality of Kazakhstan's population.

      Metabolic Surgery is the best option for treat type 2 diabetes and other components of MetS.

      Reduction of excess body weight positively affects the clinical course and life expectancy of
      patients with MetS. Currently, surgeries and physicians accumulated positive results of
      treatment of patients with MetS methods of surgical and nonsurgical weight loss. The use of
      endoscopic staplers for surgical weight loss does not exclude the emergence of serious
      complications of surgery, for example, including bleeding and leakage in the stapler suture
      line. Therefore, the advantages of using a band in the gastric bypass surgery are justified
      from a security standpoint.

      It is known that increased systemic inflammation and oxidative stress associated with obesity
      can accelerate aging and therefore telomere length (TL) can serve as an indicator of aging at
      the cellular level. Obesity has a known association with shorter TL. And weight loss in obese
      men is associated with increased telomere length. But the reduction in body weight with
      obesity changes the life expectancy remains not clear enough.

      Study design The study is designed as an interventional, prospective, randomized, controlled,
      single-center clinical trial. Patient enrollment started on May 24, 2018, and the last
      patient is expected to be included in the study on September 4, 2019. The ethics committee of
      the Corporate Fund "University Medical Center" (UMC) has granted ethics approval for this
      study (May 24, 2018, Approval Number 5.

      Study population/participants and recruitment Recruitment will be carried out by responsible
      bariatric surgeons with a minimum of 10 years of bariatric experience in the Department of
      Surgery, National Scientific Center for Oncology and Transplantation (Astana, Kazakhstan).
      Screening is done on the day - 7~ 0 prior to the treatment in order to ensure that patients
      fulfill the inclusion criteria. Patients will attend an informational meeting, where they
      will be informed about the study's purpose, process, and possible profits and risks. Patients
      fulfilling the study criteria who have signed the informed consent form will start treatment
      in accordance with the standard routines of the trial site. The informed consent will be
      obtained by the investigators. During the trial, the investigators will continue to provide
      additional health care or compensation for participants' health care needs that arise as a
      direct consequence of trial participation.

      Randomization Informed consent will be obtained from each participant before patient
      enrollment in the study. Patients who meet all the inclusion criteria and none of the
      exclusion criteria will be consecutively included and randomized into one of the three study
      arms by the study statistician, who is not involved in the enrollment, assignment, or
      assessment of patients, on random allocation. Allocation concealment is ensured with the use
      of sequentially numbered, identical, opaque, sealed envelopes. The intervention will be
      assigned by a nurse, who has also no involvement in the enrollment or assessment of patients,
      who will open the sealed envelope during the visit before surgery.

        -  Group 1(A). The patients in Group 1 are treated by laparoscopic band-separated
           (stapleless) mini-gastric bypass procedure: Gastric band (absorbable ligature)
           introduced in the abdomen and retracted through the retro-gastric tunnel. Mobilization
           gastric fundus and creates obstructive gastroplication.

        -  Group 2(B). The patients in Group 2 are treated by Linear cutter stapler-separated
           mini-gastric bypass (MGB/OAGB): standard surgery.

        -  Group 3(C). The patients in Group 3 are treated by hypocaloric diet therapy with energy
           restriction (-500 kcal/d).

      Blinding In this study, the single-party independent evaluation method is used to evaluate
      the outcomes of the study. The Outcome analyzer and the study statistician are in the masking
      state.

      General procedure and monitoring Data collection and management Treatment-related data are
      collected at V1 (before intervention), at V2 (start of intervention). Follow-up data
      according to the study protocol will be followed from V1 to months 6 (V3) and 12 (V4). Data
      collection begins on the day a participant signs the informed consent and continues until the
      termination of the trial or until the participant withdraws from the trial at any time for
      any reason. If participants discontinue or deviate from the study protocols, the
      investigators will make best efforts to keep all missing data to a minimum. All original data
      are kept in chronological order for verification. Original data are timely transferred to a
      paper-based case report form (CRF) and an electronic database system located in a guarded
      facility at the trial site. Access to the study data is restricted. The PI will have access
      to the final dataset. All data files have a complete audit trail.

      Statistical methods Sample size The sample size of this superiority trial was estimated based
      on the literature and our own unpublished data.

      Data analysis Normally distributed variables will be expressed as their mean and standard
      deviation (SD) and non-normally distributed variables will be expressed as their median and
      interquartile range; categorical variables will be expressed as the sample size number plus a
      percentage (n, %). In test groups of continuous normally distributed variables, the Student
      t-test will be used; the Mann-Whitney U test will be used for continuous non-normally
      distributed data. Categorical variables will be compared with the χ2 test or Fisher's exact
      test or, when appropriate, as the relative risk. Statistical analysis will be conducted on an
      intention-to-treat (ITT) basis. The multivariable analysis will be conducted by logistic
      regression and a generalized mixed linear regression model to take into account any possible
      confounding covariate adjustments necessary, and also to consider within-center variability.
      A p-value of < 0.05 will be considered statistically significant.

      Populations for evaluation and missing data management

      All evaluations, in particular, the evaluation of the primary outcome measure, will be made
      on the basis of all randomized patients, regardless of whether or not they adhered to the
      treatment protocol or provided complete data sets. In particular, these latter patients are
      those:

      Who discontinued the clinical trial; they will be evaluated as if they had complied with it
      Whose planned examinations were not carried out within the planned timeframe; they will still
      be taken into consideration in the analysis Patients who withdraw their consent to use their
      personal data for statistical analyses will be excluded from the analysis.

      Missing reports of individual responses on the Quality-of-Life Questionnaire II will be
      replaced by simple imputation according to the recommendations of the test manual.

      The reason for the missing data will be analyzed, and the data missing at random will be
      handled with multiple imputations and model-based approaches, such as mixed models or
      weighted generalized estimating equations (GEEs) for repeatedly measured outcomes.
      Sensitivity analysis will be performed to examine the robustness of the results to
      assumptions made in the complete case analysis.

      Adverse events An adverse event (AE) refers to any untoward event that occurs during the
      clinical study but does not necessarily have a causal relationship with surgical treatment.
      Safety evaluation is carried out from the point at which the signature of the informed
      consent is obtained until the end of the study or until patient withdrawal from the trial,
      according to management requirements. Adverse events or serious adverse events should be
      reported.

      A serious adverse event (SAE) refers to an event that causes hospitalization, prolonged
      hospitalization, disability, incapacity, life-threatening illness or death, or congenital
      malformation during the clinical trial.

      During the study, all AEs are recorded. Records include the name of the AE (using standard
      medical terminology), the date of the AE occurrence, and disappearance/stability, severity,
      impact on the surgery, relationship with the surgery, treatment measures, and outcomes. If an
      SAE occurs, researchers fill in an SAE Report. The report is signed and dated and reported to
      the ethics committee of the Corporate Fund "University Medical Center" (UMC) and the clinical
      research center of the National Scientific Center for Oncology and Transplantation (Astana,
      Kazakhstan) within 24 h.

      Quality control All surgeons and analyzers will be required to undergo special training prior
      to the trial to guarantee consistent practice. The training program will include diagnosis,
      inclusion/exclusion/exit criteria, surgery techniques, follow-up procedures, and completion
      of CRFs. The trial will be monitored by quality assurance personnel from the clinical
      research center of the National Scientific Center for Oncology and Transplantation, who will
      be independent of the study team, and an independent steering committee. There will be
      periodic monitoring to guarantee accuracy and quality throughout the study period. The
      essential documents (consent information, enrollment, protocol deviations, number and
      proportion of missed visits, and losses to follow-up) will be monitored and checked for
      accuracy and completeness by the monitors.
    

Intervention name(s): Laparoscopic one anastomosis gastric bypass; Hypocaloric diet therapy
Intervention type(s): Procedure; Dietary Supplement
Intervention description(s): Laparoscopic surgical bariatric procedure with creation gastric pouch. A jejunal loop was created about 200 cm from the ligament of Treitz and anastomosed to the gastric pouch.; Hypocaloric diet therapy with energy restriction (-500 kcal/d)
Other intervention name(s): MGB/OAGB; mini-gastric bypass
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are randomly allocated to one of three groups:
Surgical bariatric procedure in the first (A) group undergo the laparoscopic stapleless-separated mini-gastric bypass procedure: Gastric band (absorbable ligature) was introduced in the abdomen and retracted through the retrogastric tunnel. Mobilization and displacement of gastric fundus and create obstructive gastroplication. Hand-sewn gastrojejunostomy completes the intervention.
Surgical bariatric procedure in the second (B) group: Linear cutter stapler-separated mini-gastric bypass (MGB/OAGB): standard surgery.
Non-Surgical interventional in three (C) group including hypocaloric diet therapy.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Obesity; Bariatric surgery; Ospanov's procedure; One anastomosis gastric bypass; Stapleless - separated gastric bypass; Weight loss therapy; Metabolic syndrome; Life expectancy; Telomere lenght; Hypocaloric diet