Clinical trial NCT06092515: Efficacy of Zinc Fortified Fermented Wheat Flour
Official title: EZAFFAW - Efficacy of Zinc Fortified Fermented Wheat Flour: Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malnutrition
Diabetes
Inflammation
Conjunctivitis
Keywords: Zinc
Fortification
Micronutrient
Flour
Trial
Deficiencies
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: Bahauddin Zakariya University
name: University of California
name: The Hospital for Sick Children
First posted: 2023-10-23
Enrollment: 1044
Sex: ALL
Minimum age (years): 10
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: Inclusion Criteria:

* Adolescents aged 10-19 years
* Adult women aged 20-40 years.
* Wheat as a staple part of their diet

Exclusion Criteria:

* Severe Malnutrition
* Pregnant or Lactating
* Chronic Diseases
* Participation in Similar Programs
* Individuals taking vitamin or mineral supplements at the time of enrollment
* Planned Relocation from the study area within the next 6-7

Primary outcomes:
measure: Zinc Status
timeFrame: Baseline and six months post intervention
measure: Fasting Blood Glucose
timeFrame: Baseline and six months post-intervention.
measure: HbA1C Levels
timeFrame: Baseline and six months post-intervention.
measure: Insulin Levels
timeFrame: Baseline and six months post-intervention.
measure: Lipid Profiles
timeFrame: Six months post-intervention.
measure: Zinc Deficiency (%)
timeFrame: Baseline and six months post intervention
measure: Red blood cell membrane fatty acids concentrations
timeFrame: At six months post intervention
Secondary outcomes:
measure: Change in Weight (kg)
timeFrame: Six months post intervention
measure: Change in Height (m)
timeFrame: Six months post intervention
measure: Change in BMI (kg/m²)
timeFrame: Six months post intervention
measure: Acceptability and Adherence Assessment
timeFrame: Six months post intervention
measure: School Attendance and Academic Performance
timeFrame: Six months post intervention
measure: Morbidity
timeFrame: Six months post intervention
measure: Anemia
timeFrame: Six months post intervention
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan University
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Jai K Das
role: PRINCIPAL_INVESTIGATOR
References: