EZAFFAW: Efficacy of Zinc Fortified Fermented Wheat Flour

Sponsor

Aga Khan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06092515

Collaborator

Bahauddin Zakariya University (Other), University of California (Other), The Hospital for Sick Children (Other)

1,200

Enrollment

Location

Arms

15.9

Anticipated Duration (Months)

75.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Zinc is a pivotal micronutrient that participates in numerous essential metabolic pathways within the human body. Its multifaceted role makes the manifestations of zinc deficiency remarkably nonspecific and age-dependent. In children, zinc deficiency can manifest as growth retardation, cognitive impairment, recurrent infections, and other diverse symptoms. Adolescents and adults may experience fertility issues, work capacity impairment, and metabolic disorders due to zinc deficiency. Furthermore, zinc plays a crucial role in maintaining immune function, particularly in the elderly, where recurrent infections can be a notable outcome of deficiency. Given its fundamental importance, the potential benefits of zinc supplementation and fortification strategies have been explored, with some evidence indicating positive effects on health outcomes such as childhood mortality, diarrhea morbidity, and even risk factors for conditions like Type 2 Diabetes (T2DM) and cardiovascular disease (CVD). Understanding zinc's significance in these metabolic processes is vital for addressing deficiencies and improving public health.

A study is needed to assess the effect of various types of fermented and unfermented wheat flour flatbread and its impact on health including zinc status, anthropometric outcomes, risk of T2DM and CVD and morbidity on adolescent and adult females. The whole wheat flatbread trial would be ideal to inform policy as it is regularly consumed in Sindh as most people rely on chakki for wheat grinding and it is used commonly to make roti at home.

Condition or Disease	Intervention/Treatment	Phase
Malnutrition Diabetes Inflammation Conjunctivitis	Dietary Supplement: Fermented High Zinc Wheat Flour Flatbread Dietary Supplement: Unfermented High Zinc Wheat Flour Flatbread Dietary Supplement: Post-Harvest Fortified Whole Wheat Flour Flatbread Dietary Supplement: Low Zinc Whole Wheat Flour Flatbread (Control Group)	N/A

Detailed Description

STUDY DESIGN

This will be an individually randomized, double-blind efficacy trial in Mithi, District Tharparkar, Sindh, Pakistan. This district is among the most impoverished in Sindh, characterized by a tropical desert climate with extremely hot mornings. Approximately 87% of the population in Tharparkar lives below the poverty line. Due to its challenging demographics and environmental conditions, the region has endured severe droughts and faces the highest level of food insecurity among Sindh districts. It is concerning that 60% of children under five years suffer from stunting, 33.3% from wasting, and nearly 19.8% experience both conditions simultaneously. Additionally, approximately 40.4% of non-pregnant women of reproductive age are underweight. Tharparkar has been selected for this study due to its alarming rates of malnutrition and micronutrient deficiencies, making it an ideal location to assess the effectiveness of fortified wheat flour.

RESEARCH QUESTION

Primary Does consumption of whole wheat flatbread made with fermented and unfermented 'high zinc wheat' or with 'post-harvest zinc-fortified wheat flour' improve zinc status and metabolic health among adolescents (10-19 years) and adult women (20-40 years) at high risk of zinc deficiency and T2DM compared to 'low zinc' whole wheat flatbread?
Secondary Does an increase in bioavailable dietary zinc intake improve indicators for predicting the risk of T2DM in adolescents and adult women at high risk of zinc deficiency? SPECIFIC OBJECTIVES
Primary To evaluate the efficacy of whole wheat flatbread made with fermented and unfermented 'high zinc wheat' or post-harvest zinc-fortified wheat on zinc status/zinc deficiency and metabolic health among adolescents and adult women at high risk of zinc deficiency when compared to the 'low zinc' whole wheat flatbread.
Secondary To assess if an increase in bioavailable dietary zinc intake improves indicators for predicting the risk of T2DM in adolescents and adult women at high risk of zinc deficiency.

PARTICIPANTS The study will include adolescents (10-19 years) and adult women (20-40 years) INTERVENTION

Participants will be randomly divided into four groups according to the four-arm design in a 1:1:1:1 ratio. A total of 1000 participants would be randomly allocated to each of the groups in a 1:1:1:1 ratio.

Group 1: will receive fermented high zinc wheat flour flatbread
Group 2: will receive unfermented high zinc wheat flour flatbread
Group 3: will receive fortified (post-harvest) whole wheat flour flatbread
Group 4: will receive low zinc whole wheat flour flatbread

It would be a six-month intervention, where the participants would be given flatbread with a vegetable/pulse (daal) each day for six days a week for six months. On average, 2-3 flatbreads will be provided per participant (this was ascertained in the pilot activity). This would be provided at the school/college campus at lunch time i.e., at 1.30pm and all the participants enrolled in the study would be directly observed each day for the amount consumed and adult women would be provided meal at a community place.

OUTCOMES

Primary:

Serum zinc concentration
Zinc deficiency
HbA1C
Fasting blood glucose
Insulin levels
HOMA-IR (cut-off >2) (27)
Lipid profile (total cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL); triglycerides (TGs))
Red blood cell membrane fatty acids concentrations

Secondary:

Anthropometric measurements:
Height
Weight
Mid upper arm circumference (MUAC)
Waist circumference
Body Mass Index (BMI) - Severe thinness, thinness, normal weight, overweight, obese
Blood Pressure
Anemia
School attendance/ performance
Dietary intakes through 24hr dietary recall.
Morbidity - Diarrhea, Acute respiratory infection (ARI) etc.

Compliance:

Number of days each participant had flatbread
Flatbread consumed (weight) each day

SAMPLE SIZE CALCULATION The study sample size was calculated based on an individually randomized four arm design on the primary outcome of mean serum zinc levels and HbA1c. The mean HbA1c taken was 5.62% (SD 1.96) and mean zinc was 79.5 µg/dL (SD 35.9) according to NNS-2018. The serum zinc data for the Tharparkar district was taken from NNS 2018, while there is no data on area specific estimates for T2DM and HbA1c. A recent national community-based survey conducted in 2019 found that the prevalence of diabetes (19.09%) and pre-diabetes (12.79%) in rural areas of Pakistan is high compared to the urban areas of Pakistan (diabetes: 15.75%; prediabetes: 9.89%) and the overall mean HbA1c was 5.62% (SD 1.96).

The sample size was calculated with a power of 0.8 and alpha of 0.05 to detect a difference of at least 0.12 effect size in the mean serum zinc levels between groups and to detect a 0.2 effect size in the mean HbA1c levels with a dropout rate of 10%.

The sample size calculated is 250 participants. A total of 1000 participants would be randomly allocated to each of the groups in a 1:1:1:1 ratio.

Baseline, midline, and end-line data collection.

All the participants will be assessed at baseline, and at endline. Data will be collected on socio-demographic factors, dietary intake through 24-hour dietary recall, anthropometry (weight, height, MUAC, waist circumference), blood pressures and blood samples for bio-chemical analysis including serum zinc levels, FBS, HbA1C, insulin at both baseline and endline, while lipid profile and RBC membrane fatty acids would be done at endline only. At midline, 24-hour dietary recalls, serum zinc, and HbA1C will be taken on a subset from each group. For morbidity and ARI, a two-week data collection will be carried out.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This clinical trial investigates the health impact of consuming various types of wheat flour flatbreads among adolescent and adult females. The primary focus is on assessing zinc status and metabolic health in individuals at high risk of zinc deficiency and Type 2 Diabetes (T2DM). The study encompasses both fermented and unfermented flatbreads made from wheat variants with different zinc content and "post-harvest fortified wheat flour.This clinical trial investigates the health impact of consuming various types of wheat flour flatbreads among adolescent and adult females. The primary focus is on assessing zinc status and metabolic health in individuals at high risk of zinc deficiency and Type 2 Diabetes (T2DM). The study encompasses both fermented and unfermented flatbreads made from wheat variants with different zinc content and "post-harvest fortified wheat flour.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

This clinical trial will be conducted with a double-blind design Participant Blinding: Participants will not be informed about which specific type of flatbread they are receiving. Each participant will receive their assigned flatbread without knowledge of whether it falls into the fermented high zinc, unfermented high zinc, post-harvest fortified, or low zinc category. Investigator and outcomes assessor Blinding: The investigators and research staff responsible for data collection and assessment will also be unaware of the treatment assignments. They will not be involved in the preparation of the flatbreads to ensure that their observations and assessments are unbiased.

Primary Purpose:

Prevention

Official Title:

EZAFFAW - Efficacy of Zinc Fortified Fermented Wheat Flour: Randomized Controlled Trial

Actual Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Mar 30, 2024

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fermented High Zinc Wheat Flour Flatbread Participants in this arm will receive fermented whole wheat flatbreads made from wheat variants with a high zinc content, ranging. These flatbreads are prepared through traditional fermentation methods.	Dietary Supplement: Fermented High Zinc Wheat Flour Flatbread Participants in this group will receive flatbreads made from fermented high zinc wheat flour. The flatbreads will be prepared using traditional fermentation methods. These flatbreads will be provided to participants to consume daily, along with vegetables or pulses (daal), for six days a week over the course of six months.
Experimental: Unfermented High Zinc Wheat Flour Flatbread Participants in this arm will receive unfermented whole wheat flatbreads made from wheat variants with a high zinc content. These flatbreads provide a source of bioavailable zinc without the fermentation process.	Dietary Supplement: Unfermented High Zinc Wheat Flour Flatbread Participants in this group will receive flatbreads made from unfermented high zinc wheat flour, The flatbreads will not undergo a fermentation process. These flatbreads will be provided to participants to consume daily, along with vegetables or pulses (daal), for six days a week over the course of six months.
Experimental: Fortified Wheat Flour flatbread Participants in this arm will receive flatbreads made from whole wheat flour fortified post-harvest to contain a zinc content	Dietary Supplement: Post-Harvest Fortified Whole Wheat Flour Flatbread Participants in this group will receive flatbreads made from whole wheat flour fortified post-harvest These fortified flatbreads will be provided to participants for daily consumption, along with vegetables or pulses (daal), for six days a week over the course of six months.
Active Comparator: Low Zinc Wheat flatbread Participants in this arm will receive whole wheat flatbreads made from wheat variants with a low zinc content	Dietary Supplement: Low Zinc Whole Wheat Flour Flatbread (Control Group) Participants in this group will serve as the control group. They will receive flatbreads made from whole wheat flour with a low zinc content These low zinc flatbreads will be provided to participants for daily consumption, along with vegetables or pulses (daal), for six days a week over the course of six months. six days a week over the course of six months.

Outcome Measures

Primary Outcome Measures

Zinc Status [Baseline and six months post intervention]
The primary outcome is the measurement of serum zinc status (micrograms per deciliter (μg/dL) in participants. This includes assessing the concentration of zinc in serum samples. Changes in serum zinc levels will be compared between the four intervention groups.
Fasting Blood Glucose [Baseline and six months post-intervention.]
This outcome assesses changes in participants' fasting blood glucose levels, measured in milligrams per deciliter (mg/dL). It aims to understand alterations in blood glucose levels resulting from flatbread interventions.
HbA1C Levels [Baseline and six months post-intervention.]
This measure evaluates HbA1C levels, expressed as a percentage (%). It provides insights into long-term blood glucose control, helping assess the impact of dietary interventions.
Insulin Levels [Baseline and six months post-intervention.]
This measure assesses participants' insulin levels, measured in microunits per milliliter (μU/mL). It helps in understanding changes in insulin sensitivity as a result of dietary interventions.
Lipid Profiles [Six months post-intervention.]
This measure assesses participants' lipid profiles, with the unit of measure to be specified (e.g., milligrams per deciliter, mg/dL). It provides insights into changes in lipid levels and their potential effects on overall body composition due to dietary interventions.
Zinc Deficiency (%) [Baseline and six months post intervention]
This primary outcome evaluates the prevalence of zinc deficiency among participants and it would be compared across the four groups.
Red blood cell membrane fatty acids concentrations [At six months post intervention]
This outcome measures the red blood cell membrane fatty acids concentrations as a percentage (%) and This would be compared across the four groups.

Secondary Outcome Measures

Change in Weight (kg) [Six months post intervention]
This outcome assesses changes in participants' weight, measured in kilograms (kg), to understand alterations in their physical characteristics resulting from flatbread interventions.
Change in Height (m) [Six months post intervention]
This measure evaluates changes in participants' height, measured in meters (m), to determine any variations in their physical stature due to dietary changes.
Change in BMI (kg/m²) [Six months post intervention]
Body Mass Index (BMI) is calculated using weight (in kilograms) and height (in meters) and is measured in kg/m². This measure provides insights into participants' overall body composition and potential effects of dietary changes.
Acceptability and Adherence Assessment [Six months post intervention]
Secondary outcomes focus on participants' satisfaction and adherence to dietary interventions, offering insights into the feasibility and acceptability of the intervention.
School Attendance and Academic Performance [Six months post intervention]
This outcome aims to determine if the intervention resulted in better school attendance and academic performance (determined by school) among participants.
Morbidity [Six months post intervention]
This outcome monitors the incidence of common health infections as diarrhea and acute respiratory infections and will be reported as a percentage (%).
Anemia [Six months post intervention]
Anemia will be assessed through hemoglobin levels and will be reported as a percentage (%). This will determine whether there was a difference among the four groups.