Effect of Weight Loss on Hepcidin Levels and Iron Status in Subjects With Obesity.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06104800

Collaborator

(none)

Enrollment

Arms

11.7

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Obesity and iron deficiency are the nutritional disorders with the highest prevalence worldwide. Different mechanisms have been proposed to explain iron deficiency secondary to obesity. Among the most studied is the deficit in dietary iron intake or the increase in blood volume that increases the need for the metal. However, one of the most plausible mechanisms linking obesity and iron deficiency is low-grade systemic inflammation, through the iron metabolism intermediate known as hepcidin. The investigators objective is to evaluate the effect of weight loss by caloric restriction on hepcidin and serum iron concentration in people living with obesity and iron deficiency. The study will be divided into two phases: Phase 1: A cross-sectional study (cases and controls) to compare hepcidin levels, iron status and inflammatory markers in people living with and without obesity. The second phase consists of an open-label randomized controlled clinical trial. Individuals living with obesity who are iron deficient will be recruited and randomized to one of 2 dietary intervention groups with 60-day follow-up. The intervention groups will be: diet with caloric restriction rich in protein (with red meat) and diet with caloric restriction rich in protein (without red meat). Hepcidin levels, iron status and inflammatory markers will be determined at the beginning and end of the intervention. The nutritional intervention will have the following distribution of macronutrients in the diet: protein 1.5 g/kg of ideal weight, 50% carbohydrates and 25-30% fats.

Condition or Disease	Intervention/Treatment	Phase
Obesity Iron Deficiency Anemia	Other: Calorie-restricted diet with red meat Other: Calorie-restricted diet without red meat	N/A

Detailed Description

The study will consist of two phases: Phase 1, which will be cross-sectional, and Phase 2, which will involve a randomized controlled clinical trial.

Phase 1: Cross-Sectional Study A cross-sectional study will be conducted to compare hepcidin levels, iron status and inflammatory markers in people living with and without obesity. Upon obtaining signed consent, participants will undergo a medical history assessment, anthropometric measurements (weight, height, waist circumference), body composition analysis (% body fat, % skeletal muscle mass, % fat-free mass), and blood samples will be collected to determine serum hepcidin levels, iron status, inflammatory markers (C-reactive protein, interleukin-6, lipopolysaccharides), and oxidative stress markers (MDA).

Additional blood samples will be taken for biochemical tests (glucose, lipid profile, creatinine, urea, liver function tests), insulin, leptin, adiponectin, and, optionally, DNA isolation for polymorphisms determination and those associated with iron metabolism and obesity. Participants will also complete a food frequency questionnaire (SNUT).

Phase 2: Open randomized controlled clinical trial This phase will be conducted to assess the impact of weight loss on hepcidin levels, iron status, and inflammatory markers in individuals living with obesity. Participants recruited for this phase will be selected from those identified in the first phase who exhibit iron deficiency (serum iron < 50 mcg/dL).

Participants will be randomly assigned to one of two dietary intervention groups, both of which will undergo a 60-day follow-up period with a calorie-restricted diet, reducing caloric intake by less than 25% of the resting energy expenditure determined by indirect calorimetry.

The intervention groups will be as follows:

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (including red meat), 50% carbohydrates, and 25-30% fats.
Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (excluding red meat), 50% carbohydrates, and 25-30% fats.

Additionally, all participants will receive ferrous sulfate 200mg every 48 hours for three months to correct iron-deficiency anemia.

During the initial and final visits, participants will undergo a 24-hour dietary recall, complete a physical activity questionnaire, and fill out a quality-of-life questionnaire. Additionally, anthropometric measurements and body composition analysis will be conducted. Blood samples will be collected to determine various biochemical parameters in the blood, including lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides), liver function tests, glucose, insulin, creatinine, urea, oxidative stress markers, inflammatory markers (C-reactive protein and lipopolysaccharides), and iron status markers. Furthermore, stool samples will be collected to analyze the composition of the intestinal microbiota and metabolomics.

To assess treatment adherence, participants will be provided with a food logs to record their daily food consumption during the initial visit. The participants will also receive a pantry containing protein-rich foods every week to facilitate the nutritional intervention. Also, 2 phone calls will be made each week to evaluate adherence to treatment. The adherence will be determined with the % of adherence to the dietary treatment as obtained in the analysis of the food logs.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The groups will receive the treatment simultaneously.The groups will receive the treatment simultaneously.

Masking:

Single (Outcomes Assessor)

Masking Description:

The person who will perform the biochemical determinations and the statistical analysis will be blinded from the intervention group by assigning each patient.

Primary Purpose:

Treatment

Official Title:

Effect of Weight Loss on Hepcidin Levels and Iron Status in Subjects With Obesity.

Anticipated Study Start Date :

Jan 8, 2024

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Red meat diet Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (including red meat), 50% carbohydrates, and 25-30% fats.	Other: Calorie-restricted diet with red meat Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (including red meat), 50% carbohydrates, and 25-30% fats.
Active Comparator: Red meat free diet Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (excluding red meat), 50% carbohydrates, and 25-30% fats	Other: Calorie-restricted diet without red meat Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (excluding red meat), 50% carbohydrates, and 25-30% fats

Arm

Intervention/Treatment

Experimental: Red meat diet

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (including red meat), 50% carbohydrates, and 25-30% fats.

Other: Calorie-restricted diet with red meat

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (including red meat), 50% carbohydrates, and 25-30% fats.

Active Comparator: Red meat free diet

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (excluding red meat), 50% carbohydrates, and 25-30% fats

Other: Calorie-restricted diet without red meat

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (excluding red meat), 50% carbohydrates, and 25-30% fats

Outcome Measures

Primary Outcome Measures

Serum hepcidin concentration in mcg/dL [Baseline to 2 months of intervention]
Change in serum hepcidin concentration between different nutritional interventions in subjects with obesity and iron deficiency

Secondary Outcome Measures

Serum iron concentration in mcg/dL [Baseline to 2 months of intervention]
Change in serum iron concentration between different nutritional interventions in subjects with obesity and iron deficiency
Serum ferritin concentration in ng/mL [Baseline to 2 months of intervention]
Change in serum ferritin concentration between different nutritional interventions in subjects with obesity and iron deficiency
Serum iron binding capacity concentration in mcg/dL [Baseline to 2 months of intervention]
Change in serum iron binding capacity concentration between different nutritional interventions in subjects with obesity and iron deficiency
Blood reticulocytes percentage [Baseline to 2 months of intervention]
Change in blood reticulocytes percentage between different nutritional interventions in subjects with obesity and iron deficiency
Serum soluble transferrin receptor concentration in mg/L. [Baseline to 2 months of intervention]
Change in serum soluble transferrin receptor concentration between different nutritional interventions in subjects with obesity and iron deficiency
Blood haemoglobin concentration in g/dL [Baseline to 2 months of intervention]
Change in blood haemoglobin concentration between different nutritional interventions in subjects with obesity and iron deficiency
Serum C-reactive protein concentration in g/dL [Baseline to 2 months of intervention]
Change in C-reactive protein concentration between different nutritional interventions in subjects with obesity and iron deficiency
Serum leptin concentration in ng/mL [Baseline to 2 months of intervention]
Change in leptin concentration in the serum determined by ELISA kit between different nutritional interventions in subjects with obesity and iron deficiency
Serum interleukin 6 concentration in pg/mL [Baseline to 2 months of intervention]
Change in interleukin-6 concentration determined by ELISA kit between different nutritional interventions in subjects with obesity and iron deficiency
Serum lipopolysaccharides concentration in ng/mL [Baseline to 2 months of intervention]
Change in lipopolysaccharides concentration between different nutritional interventions in subjects with obesity and iron deficiency
Plasma malondialdehyde concentration in nmol/mL [Baseline to 2 months of intervention]
Change in malondialdehyde concentration by spectrophotometry between different nutritional interventions in subjects with obesity and iron deficiency
Plasma trolox equivalents concentration in umols/mL [Baseline to 2 months of intervention]
Change in trolox equivalents concentration between different nutritional interventions in subjects with obesity and iron deficiency
Changes in faecal microbiota composition [Baseline to 2 months of intervention]
The change in faecal microbiota composition shall be measured by 16 ribosome sequencing at baseline and at 2 months. The relative change of each bacterial taxon shall be calculated on the basis of the abundance of the given bacteria at baseline to 2 months between different nutritional interventions in subjects with obesity and iron deficiency
Serum total cholesterol concentration in mg/dL [Baseline to 2 months of intervention]
Change in total cholesterol concentration determined by autoanalyzer between different nutritional interventions in subjects with obesity and iron deficiency
Serum LDL cholesterol concentration in mg/dL [Baseline to 2 months of intervention]
Change in LDL-cholesterol concentration determined by autoanalyzer between different nutritional interventions in subjects with obesity and iron deficiency
Serum triglycerides concentration in mg/dL [Baseline to 2 months of intervention]
Change in triglycerides concentration determined by autoanalyzer between different nutritional interventions in subjects with obesity and iron deficiency
Serum aspartate aminotransferase concentration in IU/mL [Baseline to 2 months of intervention]
Change in aspartate aminotransferase concentration determined by autoanalyzer between different nutritional interventions in subjects with obesity and iron deficiency
Serum alanine aminotransferase concentration in IU/mL [Baseline to 2 months of intervention]
Change in alanine aminotransferase concentration determined by autoanalyzer between different nutritional interventions in subjects with obesity and iron deficiency
Serum glucose concentration in mg/dL [Baseline to 2 months of intervention]
Change in serum glucose concentration determined by autoanalyzer between different nutritional interventions in subjects with obesity and iron deficiency
Body weight in kilograms [Baseline to 2 months of intervention]
Change in body weight between different nutritional interventions in subjects with obesity and iron deficiency
Fat mass percentage [Baseline to 2 months of intervention]
Change in fat mass percentage determined by multifrequency electrical bioimpedance between different nutritional interventions in subjects with obesity and iron deficiency
Waist circumference in centimeters [Baseline to 2 months of intervention]
Change in waist circumference between different nutritional interventions in subjects with obesity and iron deficiency
Lean mass percentage [Baseline to 2 months of intervention]
Change in fat mass percentage determined by multifrequency electrical bioimpedance between different nutritional interventions in subjects with obesity and iron deficiency
Skeletal muscle mass percentage [Baseline to 2 months of intervention]
Change in fat mass percentage determined by multifrequency electrical bioimpedance between different nutritional interventions in subjects with obesity and iron deficiency

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Phase 1

Signing of the informed consent form
Both sexes
Adults over 18 years of age
BMI of 18.5 and under 40 kg/m2

Phase 2

Both sexes
Adults older than 18 years
People with obesity (BMI of 30 to 40 kg/m2) and serum iron < 50 micrograms/dL.
Total cholesterol less than 240 mg/dL (with the diet plan 20% decrease).

Exclusion Criteria:

Any type of diabetes.
Patients with renal disease diagnosed by a physician.
Patients with acquired diseases that secondarily produce obesity and diabetes.
Patients who have suffered a cardiovascular event.
Weight loss > 3 kg in the last 3 months.
Patients with catabolic diseases such as cancer and acquired immunodeficiency syndrome.
Pregnancy.
Treatment with any drug treatment:

Treatment with antihypertensive drugs (loop or potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers, alpha blockers, calcium antagonists, beta blockers).
Treatment with hypoglycemic agents (sulfonylureas, biguanides, incretins) or insulin and antidiabetics.
Treatment with statins, fibrates or other drugs to control dyslipidemia.
Use of steroid drugs, chemotherapy, immunosuppressants or radiotherapy.
Anorectics or drugs that accelerate weight loss.
Any drug or medication that activates intestinal motility (cisapride, dimethicone, domperidone, metoclopramide, trimebutine).
Laxatives or antispasmodics 4 weeks prior to the study h) Antibiotic treatment 2 months prior to the study.

Patients who have suffered a blood loss of more than 500 ml or recent gastrointestinal tract perforation.
Patients with a smoking index greater than 21.
Consumption of large amounts of alcohol (14 drinks for women or 21 drinks for men in a normal week).
Consumption of any recreational psychoactive substance.
Treatment with any medication that influences inflammation or iron metabolism (proton pump inhibitors, antacids, bisphosphonates, bile acid or calcium sequestrants).
Patients who are vegetarians
Allergy or intolerance to any food mentioned in the proposed pantry such as egg, dairy, fish, tuna, chicken, beans, lima beans and/or lentils.
Unwillingness to consume any of the foods listed in the proposed pantry.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Investigators

Principal Investigator: Martha Guevara-Cruz, MD, PhD, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Martha Guevara Cruz, Principal Investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

ClinicalTrials.gov Identifier:

NCT06104800

Other Study ID Numbers:

FNU-4686-23-24-1

First Posted:

Oct 27, 2023

Last Update Posted:

Oct 27, 2023

Last Verified:

Oct 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Anemia, Iron-Deficiency

Obesity

Iron Deficiencies

Weight Loss

Study Results

No Results Posted as of Oct 27, 2023