Effect of Sea Grapes-antioxidants Extract in Obese Men : 4 Weeks Randomized-Double Blind Controlled Trial
Condition: Obesity; Aging; Diabetes
MeSH terms: Obesity
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Doses of 150 mg/kg BW (30 mg/200g BW) sea grape extract in a previous pre-clinical trial,
      showed that it could improve blood glucose, total cholesterol and serum PGC-1 levels in rats
      fed a diet high in fat and cholesterol. In addition, you also have hepatoprotective activity
      (aka non-toxic) in diabetic mice. Previous research, is an in vivo (Pre-clinical) study that
      has not represented the benefits or efficacy of sea grape extract on variables tested in
      humans. Therefore, this clinical trial was conducted to support the effect of sea grape
      extract-antioxidant on blood glucose, total cholesterol, and PGC-1 levels in obese men for 4
      weeks using a Randomized-Double Blind Controlled Trial.
    

Detailed description: 
      The study was a 4-week, randomized, double-blind, placebo-controlled clinical trial followed
      by a 1-week screening period. Participants who respond to the invitation and meet the entry
      criteria during the telephone screening interview are scheduled for the initial visit.
      Evaluation during the initial visit includes physical examination in the form of BMI (Body
      Mass Index) based on Asia-Pacific guidelines and blood parameter screening tests in the form
      of blood glucose, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein
      (LDL) and total cholesterol, and PGC-1α were performed on all participants within 1 week of
      the initial screening. A random number between 1 and 70 was generated for each subject and
      registered participants were scheduled for their first visit and randomly assigned to the sea
      grape extract group (n=35) or placebo (n=35). Sea grape extract/placebo tablets/capsules were
      given to participants every 1 week (1 day of consumption per oral) 15 Minutes before eating
      (According to the diabetes drug guidline consumtion).

      During the 4-week intervention period, participants were asked to continue their usual diet
      and not to consume functional foods or other dietary supplements. Anthropometry (BMI), Waist
      Hip Ratio (WHR) , blood parameters, urine profile (Marker of toxicity), and nutrient intake
      of both groups were measured before and after the intervention period. During the trial
      phase, all participants were instructed to maintain their normal diet and physical activity.
      Each week participants were asked to report assessments of side effects or changes in
      training, lifestyle, or diet; and to evaluate tablet compliance.

      Subjects/Participants The study participants were recruited during 2021 at Manado, Republic
      of Indonesia. A total of 150 participants agreed to participate in the study. Only
      individuals men who are obese (BMI ≥ 25 kg m-2 and Waist Hip Ratio (WHR) ≥ 0.90) according to
      Asia-Pacific guidelines and have not been diagnosed with other diseases were included in the
      study. To meet guidelines for evaluating the efficacy of functional food referring to the
      Korea Food and Drug Administration (because Indonesia does not yet exist and Koreas belong to
      one Asian region so used), very obese participants (BMI ≥ 30 kg m-2) were not included in the
      study.

      In total, 70 participants met the research criteria (age 29.98 ± 3.26 year; weight, ..... ±
      .... kg; BMI, .... ±.... kg m-2) and were randomly divided into two groups (n = 35 each)
      given sea grape extract 1.68 g/70kg BB day-1) or placebo (1.68 g/70kg BB day-1). The
      exclusion criteria for this study are as follows: (a) significant weight variation (over 10%)
      in the last 3 months; (b) a history of cardiovascular disease including arrhythmia, heart
      failure, or myocardial infarction, diabetes mellitus (DM) and the use of pacemakers; (c) a
      history of conditions that may interfere with test products or inhibit their absorption such
      as gastrointestinal diseases (Crohn's disease) or surgeries that have been experienced
      (caesarean section or enterocele); (d) participation in other clinical trials in the last 2
      months; (e) abnormal liver function; (f) a history of kidney disease (eg, acute or chronic
      renal failure and nephrtic syndrome); (g) undergo antipsychotic drug therapy within the last
      2 months; (h) laboratory test results as well as medical or psychological conditions that may
      interfere with successful participation in research assessed by researchers; (i) a history of
      alcohol or substance abuse; and (j) allergy or hypersensitivity to any of the ingredients in
      the test product; (k) is neither a passive nor an active smoker. All participants give
      written consent before the investigation begins. The research protocol was submitted to the
      Health Research Ethics Commission (KEPK) of The General Hospital of Education Prof. Dr. RD.
      Kandou (Manado, Republic of Indonesia) online at http://sim-epk.keppkn.kemkes.go.id. All
      protocols referred to The Declaration of Helsinki and The Council for International
      Organizations of Medical Sciences (CIOMS).

      Measurement of Efficacy Results A total of 70 participants who met the research criteria were
      asked to visit the clinic once every 1 week (0th, 1st, 2nd, 3rd, and 4th/last week of the
      study period) with a total of 5 clinical visits including initial examination. During each
      visit, the use of the supplement is currently reviewed and symptoms or side effects are
      noted. During screening visits, demographic and lifestyle information is collected (age,
      alcohol consumption, and smoking habits). Medical history is taken and urine turbidity tests
      are carried out.

      The following parameters are assessed; Weight, Height, WHR and BMI during each visit. Blood
      samples were collected after a minimum of 12 hours of fasting during initial screening as
      well as in the 0, 2nd and 4th weeks of the intervention period to obtain blood glucose
      profiles, total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density
      lipoprotein (LDL) and PGC-1α. Blood samples were taken from the arm vein. The arm vein to be
      punctured is cleaned with 70% alcohol and allowed to dry. A tourniquet is placed on the upper
      arm to expose and slightly accentuate the veins. The skin is stretched over the vein with the
      fingers of the left hand so that the vein cannot move. The skin is pierced with a needle and
      syringe with the right hand until the tip of the needle enters the lumen of the vein. The
      tourniquet is removed and slowly withdraw the syringe suction until the desired amount of
      blood is obtained. A 70% alcohol swab is placed over the needle and the syringe and needle
      are removed. The needle is removed from the syringe and the blood sample is transferred into
      a vacutainer tube.

      Evaluation of Safety and Diet

      The safety of the extract is assessed by the following procedure. Urine Test Strips 10 Verify
      Parameters, Parameters examined are:

        -  Glucose (50 -100 mg / dl)

        -  Protein (7.5 - 15 mg / dl)

        -  pH (5-9)

        -  Leukocytes (9-15 leu / ul)

        -  Nitrite (0.05-0.1 mg/ dl)

        -  Urobilinogen (0.2-1.0 mg / dl)

        -  Blood (5-10 Ery/ul)

        -  Ketones (2.5-5 mg/dl)

        -  Bilirubin (0.4-1.0 mg/ dl)

        -  Specific Gravity (SG) (1,000-1,030) Test the urine parameters above using Urinalysis 10U
           Reagent Strips Verify (REF U031-102 exp. 2022-03-05). Pulse rate and blood pressure are
           measured on each visit after a 5-minute break using intelliVue MP70 (Philips,
           Netherlands). Personal reports are also recorded at these times. We kept the subjects
           maintaining their usual diet and activity, and all participants completed diet records
           on each visit to the clinic during the intervention period to evaluate their energy
           intake and diet quality. Food intake data were analyzed by a nutritionist (Melvin Junior
           Tanner, S.Gz).

      Statistical Analysis Statistical analysis is performed using SPSS software, version 26 (IBM
      Corporation). Fixed effects include treatment groups, treatment visits, and interactions
      between treatment and visit groups. The value p<0.05 is considered statistically significant.
    

Intervention name(s): Sea grapes extract 1.68 g/70kg BW; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Contains antioxidants 45.66 ± 0.55% and Caulerpin. Sea grapes are usually consumed raw without any indication of poisoning.; placebo lactose powder (1.68 g/70kg BW day-1).
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study was a 4-week, randomized, double-blind, placebo-controlled clinical trial. Evaluation during the initial visit includes physical examination in the form of Body Mass Index based on Asia-Pacific guidelines and blood parameter screening tests in the form of blood glucose, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol, and PGC-1α were performed on all participants within 1 week of the initial screening. A random number between 1 and 70 was generated for each subject and registered participants were scheduled for their first visit and randomly assigned to the sea grape extract group (n=35) or placebo (n=35). Sea grape extract/placebo tablets/capsules were given to participants every 1 week (1 day of consumption per oral) 15 Minutes before eating (According to the diabetes drug guidline consumtion).
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Obesity; Aging; Functional Food; Diabetes; Dyslipidemia