MIMBLE II

COMPLETED STUDY:

MIMBLE II

MIMBLE II

Research Details

MIMBLE Study

Full title

Modifying Intestinal Integrity and Microbiome in Malnutrition with Legume-Based Feeds

The research programme included an initial pilot study, followed by the larger MIMBLE 2.0 Phase II trial.

Study overview

Severe acute malnutrition remains an important cause of childhood illness and death in sub-Saharan Africa. Standard treatment includes therapeutic milk feeds known as F75 and F100. Although these feeds support weight gain, they may not fully address the damage that severe malnutrition causes to the intestines and gut microbiome.

Children with severe malnutrition commonly experience intestinal inflammation, disruption of normal gut bacteria, lactose intolerance and impaired intestinal-barrier function. These problems may contribute to diarrhoea, poor nutrient absorption, bloodstream infections, treatment failure and death.

The MIMBLE Study investigated whether lactose-free, legume-enriched feeds containing fermentable carbohydrates could improve intestinal health while providing safe and effective nutritional rehabilitation.

Study rationale

The intestinal microbiome is the community of microorganisms that lives within the digestive system. A healthy microbiome supports digestion, immunity, nutrient production and protection against disease-causing organisms.

Severe malnutrition can reduce microbial diversity and weaken the intestinal barrier. This may allow harmful bacteria or bacterial products to cross from the intestines into the bloodstream, increasing the risk of severe infection.

Legumes contain resistant starches and other fermentable carbohydrates. Gut bacteria can ferment these carbohydrates to produce short-chain fatty acids, which may:

  • Provide energy to intestinal cells.
  • Strengthen the intestinal barrier.
  • Support beneficial gut bacteria.
  • Regulate inflammation.
  • Improve nutrient absorption.
  • Protect against disease-causing organisms.

Study objectives

The study aimed to:

  • Determine whether legume-enriched therapeutic feeds were safe and acceptable.
  • Compare nutritional recovery with standard WHO therapeutic feeds.
  • Assess whether the modified feeds improved intestinal-barrier function.
  • Examine changes in gut microbial diversity and composition.
  • Measure the production of beneficial short-chain fatty acids.
  • Assess intestinal inflammation and injury.
  • Determine whether lactose-free feeds reduced the development or duration of diarrhoea.
  • Compare survival and hospital readmission between feeding strategies.
  • Generate evidence for larger clinical trials of improved nutritional feeds.

Initial MIMBLE pilot study

The initial MIMBLE pilot study was a three-group clinical trial involving 58 Ugandan children with severe acute malnutrition.

Participants received one of the following:

  • A cowpea-enriched therapeutic feed
  • An inulin-containing therapeutic feed
  • Conventional WHO therapeutic feeds

The pilot study assessed safety, weight gain, mortality, resolution of nutritional oedema, intestinal permeability, gut inflammation, microbial diversity and production of short-chain fatty acids.

Findings from the pilot study

Weight gain, mortality and resolution of nutritional oedema were generally similar across the three feeding groups.

However, children receiving conventional feeds experienced a reduction in gut bacterial richness during the first seven days of treatment. This reduction was not observed among children receiving the cowpea-enriched feed.

The findings suggested that legume-enriched feeds could help preserve microbial diversity and intestinal fermentation during antibiotic treatment without compromising nutritional recovery. These results supported the development of the refined feed evaluated in MIMBLE 2.0. Read the published pilot-study results.

MIMBLE 2.0 study design

MIMBLE 2.0 was an open-label, proof-of-principle Phase II randomised controlled trial.

A total of 160 children were randomly assigned in equal proportions to receive either:

  • A lactose-free, chickpea-enriched therapeutic feed; or
  • Standard WHO F75 and F100 therapeutic milk feeds.

The investigational feed was designed to provide comparable amounts of energy and protein while supplying fermentable carbohydrates from chickpea flour.

Study population

MIMBLE 2.0 enrolled Ugandan children hospitalised with severe acute malnutrition.

Severe malnutrition was defined as:

  • Marasmus: mid-upper arm circumference below 11.5 cm;
  • Kwashiorkor: symmetrical pitting oedema involving at least the feet; or
  • A combination of wasting and nutritional oedema.

Children with terminal illnesses, malignant disease or other conditions associated with an extremely high risk of death were excluded.

The enrolled children had a median age of approximately 17 months. More than half presented with oedematous malnutrition.

Study site

The MIMBLE research programme was conducted in Eastern Uganda, principally at:

  • Mbale Regional Referral Hospital
  • Mbale Clinical Research Institute

The MIMBLE 2.0 protocol initially included Mbale and Soroti Regional Referral Hospitals. The reported Phase II trial was conducted at Mbale Regional Referral Hospital.

Study interventions

Standard WHO feeds

Children in the control group received F75 therapeutic milk during the stabilisation phase, followed by F100 during nutritional rehabilitation.

Legume-enriched feed

Children in the intervention group received a specially developed lactose-free nutritional paste enriched with chickpea flour.

The feed was designed to:

  • Provide energy and protein comparable to standard therapeutic feeds.
  • Reduce exposure to lactose.
  • Supply fermentable carbohydrates.
  • Promote beneficial intestinal bacteria.
  • Increase short-chain fatty-acid production.
  • Support intestinal-barrier repair.

All participants continued to receive standard inpatient management, including antibiotics, antimalarial medicines and other treatments when clinically indicated.

Study outcomes

The co-primary outcomes were:

  • Change in mid-upper arm circumference by day 90
  • Survival to day 90

Secondary outcomes included:

  • Weight gain
  • Achievement of weight gain greater than 5 g/kg per day
  • Development of new diarrhoea
  • Time to resolution of diarrhoea
  • Time to resolution of nutritional oedema
  • Hospital readmission
  • Serious adverse events
  • Changes in intestinal inflammation
  • Changes in gut microbial composition
  • Production of short-chain fatty acids
  • Changes in host and microbial metabolism

Children were assessed during hospitalisation and followed until days 28 and 90.

Main MIMBLE 2.0 findings

Nutritional recovery was similar between the two study groups. By day 90, the median increase in mid-upper arm circumference was:

  • 1.1 cm in the legume-feed group
  • 1.4 cm in the standard WHO-feed group

The difference was not statistically significant.

Day-90 mortality was also similar:

  • 11 of 80 children in the legume-feed group
  • 12 of 80 children in the standard-feed group

There were no significant differences in weight gain, development or resolution of diarrhoea, resolution of oedema or hospital readmission.

A per-protocol analysis showed numerically lower mortality and readmission among children who completed the legume-feed intervention, but the differences were not statistically significant.

Safety and acceptability

The legume-based feed produced nutritional outcomes comparable to standard WHO feeds, with no evidence of increased clinical harm.

However, some children initially found the nutritional paste less acceptable than liquid therapeutic milk. Ten children assigned to the legume-feed group were switched to standard WHO feeds because of poor early tolerance, feeding difficulty or clinical deterioration.

The study therefore demonstrated the importance of improving the taste, texture and ease of administration of future legume-based formulations.

Interpretation of the findings

The study showed that lactose-free, chickpea-enriched feeds could support nutritional recovery comparable to standard WHO therapeutic feeds. The intervention did not demonstrate a statistically significant improvement in survival, mid-upper arm circumference, diarrhoea or readmission.

Nevertheless, the study provided proof that legume-based feeds can be developed and used safely in children with severe malnutrition. The findings also identified practical improvements required before conducting larger clinical trials, particularly regarding palatability and suitability during the early stabilisation phase.

The Phase II findings were initially reported as a preprint and should therefore be described as preliminary until publication in a peer-reviewed journal. Read the MIMBLE 2.0 Phase II report.

Importance of the study

MIMBLE moved beyond measuring weight gain alone and examined the biological processes underlying recovery from severe malnutrition.

The study contributed important knowledge about:

  • Intestinal damage in severe malnutrition
  • The role of the gut microbiome in recovery
  • Fermentation of dietary carbohydrates
  • Lactose intolerance during severe illness
  • Development of culturally relevant therapeutic feeds
  • Clinical testing of locally available legumes
  • Nutritional interventions that may reduce infection and poor outcomes

The programme demonstrated the value of combining paediatric clinical research with nutrition science, microbiology, metabolomics and food-product development.

Study leadership

The MIMBLE 2.0 protocol identified:

  • Professor Gary Frost – Principal Investigator
  • Professor Peter Olupot-Olupot – Co-Principal Investigator and Mbale research lead
  • Professor Kathryn Maitland – Co-Principal Investigator
  • Dr Kevin Walsh – Co-Principal Investigator

The Mbale-based research team included William Okiror, Tonny Ssenyondo, Charles Benard Okalebo and Rita Muhindo, together with clinical, nursing, nutrition and laboratory staff.

Collaborating institutions

Participating and collaborating institutions included:

  • Mbale Clinical Research Institute
  • Mbale Regional Referral Hospital
  • Busitema University Faculty of Health Sciences
  • Imperial College London
  • King’s College London
  • MRC Clinical Trials Unit at University College London
  • KEMRI-Wellcome Trust Research Programme
  • University of Glasgow
  • University of Reading

Funding

MIMBLE 2.0 was supported through the Confidence in Concept Joint Translational Fund 2017 at Imperial College London.

Ethical approval and consent

MIMBLE 2.0 received ethical approval from:

  • Imperial College Research Ethics Committee: 17IC4146
  • Mbale Regional Referral Hospital Research Ethics Committee: COM 019/2018

Written informed consent was obtained from parents or legal guardians. An approved deferred-consent process was available for emergency situations where completing the full consent procedure could have delayed urgent treatment.

Trial registration

MIMBLE 2.0 was registered as:

ISRCTN10309022

The initial MIMBLE pilot study was registered as:

PACTR201805003381361

Study status

The MIMBLE pilot study and MIMBLE 2.0 Phase II trial are completed.

MIMBLE 2.0 recruited 160 children between July 2018 and August 2019. The pilot-study findings were published in a peer-reviewed journal in 2021, while the Phase II findings were made available as a research preprint in 2023.

Key publications

MIMBLE 2.0 Phase II findings – medRxiv preprint

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Study Summary

MIMBLE Study – Modifying Intestinal Integrity and Microbiome in Malnutrition with Legume-Based Feeds

The MIMBLE research programme investigated whether legume-enriched, lactose-free therapeutic feeds could improve recovery from severe acute malnutrition by supporting intestinal health and the gut microbiome. Following a pilot study involving 58 Ugandan children, the MIMBLE 2.0 Phase II trial enrolled 160 children at Mbale Regional Referral Hospital. The trial compared a chickpea-enriched feed with standard WHO therapeutic feeds. Nutritional recovery and survival were similar between groups, demonstrating that legume-based feeds can be used safely while highlighting the need to improve palatability and early feeding tolerance.

About

Ms. Adyango Catherine is a Human Resource Manager and Senior Grants Professional with over 15 years of experience in managing multimillion-dollar donor portfolios, project operations, and organizational systems strengthening. She currently serves as Human resource Manager at Mbale Clinical Research Institute (MCRI), where she leads in Human resource management,  donor compliance, project operations, and institutional capacity building.

At MCRI, Catherine has combined her expertise in grant management and human resources to establish efficient systems that support both research and staff welfare. She played a pivotal role in championing organizational culture reforms, developing HR policies, strengthening staff welfare schemes, and promoting inclusive recruitment processes. She also streamlined adoption of a Human Resource Management Information System (HRMIS/ESS), which reduced administrative bottlenecks and improved efficiency across teams.

Her academic background includes a Postgraduate Diploma in Human Resource Management (Uganda Management Institute), an MSc in Health Services Management, and a bachelor’s degree in business administration & management. Catherine is also pursuing ACCA training, demonstrating her commitment to continuous professional growth.

Catherine’s career reflects a strong commitment to strategic leadership, staff development, and inclusive programming, with a proven ability to balance donor expectations and human resource needs. Her work at MCRI has significantly contributed to building sustainable research capacity, enhancing compliance systems, and creating a supportive work environment that empowers both researchers and administrative staff.

About

Denis Amorut serves as the Study Site Coordinator at the Mbale Clinical Research Institute’s Soroti Site. He is a qualified Registered Nurse with a Bachelor of Science in Health Services Management from the Islamic University in Uganda and a Diploma in Comprehensive Nursing from Soroti School of Registered Comprehensive Nursing. Additionally, he is currently pursuing an Advanced Postgraduate Diploma in Clinical Research & Quality Assurance at James Lind Institute, showcasing his commitment to advancing his expertise in clinical research. Denis has an extensive professional background with 12 years in clinical nursing practice and 11 years dedicated to clinical research. He is registered with the Uganda Midwives and Nurses Council, highlighting his professional standing in the healthcare sector.
 
Throughout his career, Denis has held significant positions such as Trial Manager since November 2021 and previously as Study Site Coordinator at Soroti Regional Referral and Teaching Hospital from 2008 to October 2021. He also serves as a member of the Medicine and Therapeutic Committee at the same hospital since 2018. Denis has enriched his knowledge and skills through numerous online courses and certifications in areas like research ethics, data management for clinical studies, Good Clinical Practice (GCP), and managing health emergencies like Covid-19. His involvement in various research studies, including the TRACT study, and his roles in hospital committees further demonstrate his dedication to both practice and research in healthcare, focusing on improving patient care through evidence-based practices.

About

Ms. Linda Isabirye serves as the Public and Community Engagement Officer at MCRI, where her role encompasses a variety of tasks aimed at enhancing the Institute’s interaction with both internal and external communities. Her work is divided into two primary focuses: public engagement, where she communicates the Institute’s research and ideas to the public, and community engagement, where she assists others in conducting research and achieving their objectives.

In her community engagement efforts, Linda is involved in developing and sustaining a public engagement and involvement framework for the research program. She identifies local opportunities for community collaboration, nurturing relationships with MCRI’s research scientists, staff, and the broader community.

With over two years of experience, she has worked extensively with diverse community stakeholders. Her responsibilities include coordinating activities for the Community Advisory Board (CAB), designing, and overseeing the execution of Community Engagement (CE) initiatives. These initiatives are crucial for identifying, recruiting, and retaining volunteers, engaging community leadership, and supporting the formation and operation of community peer groups. This includes working with study participants, family support groups, and youth and adolescent groups, among others.

About

Rita Muhindo holds a MSc. Molecular Biology from Staffordshire University, UK. She attained her BSc. Biomedical Laboratory Science and Technology degree from Makerere University and an Advanced Diploma in Health Services Management from Islamic University in Uganda. She joined Mbale Clinical Research Institute in July 2011 as a laboratory technologist participating in setting up various laboratory assays for all clinical trials at the MCRI.

She is currently the laboratory manager of MCRI, a role which involves supervision all laboratory research activities at MCRI main and satellite laboratories. She has over twelve years of experience in managing laboratory clinical research and diagnostics service delivery across several key disciplines including molecular, immunology, hematology, microbiology and clinical chemistry.

She has keen interest in understanding the prevalence of red cell polymorphisms present in Ugandan donor populations. Her main focus of her MSc project was on the prevalence of Glucose-6-Phosphate dehydrogenase deficiency, α-thalassaemia and Haemoglobin S among Ugandan donors. Rita is also keen to explore the effects of these polymorphisms on the resolution of severe anaemia.

About

Dr. Charles Benard Okalebo is a highly qualified professional with a B. Pharm, an MPH, and currently a fellow in Infectious Disease and Field Epidemiology under the EDCTP-funded IDEA fellowship. His background as a pharmacist and public health specialist, combined with his role as a Quality Assurance Officer, has provided him with extensive experience in clinical research. This diverse training has honed his skills in assessing healthcare gaps, identifying problems, and designing projects to address these deficiencies. Dr. Okalebo values accuracy, integrity, quality, and career growth above all.
 
He is an experienced and determined professional in conducting clinical trials for both infectious and non-infectious diseases. With eight years in the research field, he has served as a Pharmacist and Quality Assurance Officer at the Mbale Clinical Research Institute, focusing on various types of clinical trials related to infectious diseases. His involvement spans across all phases of clinical trials (I-III), including protocol design, review, and implementation; navigating regulatory approval processes; managing investigational medicinal products (IMP); monitoring studies; establishing and implementing Quality Management processes; pharmacovigilance; and leading training sessions on the ethical conduct of research. The trials he has participated in include TRACT (ISRCTN84086586), GASTROSAM (ISRCTN76149273), PAC (ISRCTN11594437), FLACSAM (ISRCTN18051843), MIMBLE (ISRCTN10309022), and TABS (ISRCTN49726849) studies.
 
Dr. Okalebo is a dedicated researcher with a keen interest in advancing his career in pharmaco-epidemiology, statistics, and pharmacovigilance.

About

Felix Opio joined the Mbale Clinical Research Institute (MCRI) in April 2014 as Data Manager under the REACH (Realizing Effectiveness Across Continents with Hydroxyurea) ClinicalTrials.gov NCT01966731) which is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, long-term risks and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries (Mable Uganda,Kilifi Kenya, Luanda Angola and Kinshasa DRC).

He holds a Bachelor of Science in Computer Science from Gulu University, a post graduate diploma in Monitoring and Evaluation from Uganda Management Institute (UMI), Certificate in Project Management Professional from Devimpact Institute Kenya and various other certification in Clinical database development.

He Has 9 years of experience in Clinical Database design and Management, He is Currently overseeing data management work for the REACH study and all the day to day activities of the Project, He is also a member of the internal Clinical Trial Monitoring Unit and A chairperson Procurement Committee for Mbale Clinical Research Institute.

About

Ebitu Caleb Daniel serves as an I.T Support Officer at the Mbale Clinical Research Institute. He is recognized as an accomplished network and systems administrator, who takes pleasure in applying his skills to support and contribute to the technological advancement of research within the institution.
 
Ebitu graduated from Uganda Christian University Mukono with a Bachelor’s degree in Computer Science. Over the years, he has also acquired various certifications including CCNA, Information Security, Google Cloud Developer, PMP (Telecom), and Federated Identity Management.

About

Laban has accumulated over four years of experience in managing research financial processes since joining the Mbale Clinical Research Institute on July 1, 2019, as an Accounts Assistant. This experience complements his extensive background of over ten years in the banking sector, where he has previously worked for two banks in roles involving people management, cash management, internal controls, and accountability.

He holds a Bachelor’s degree in Business Studies, specializing in Accounting, from the Islamic University of Uganda. He is currently pursuing a Certificate of Public Accountants (CPA) from the Institute of Certified Public Accountants of Uganda (ICPAU), with only two papers remaining to complete the course.

Driven by an ambition to advance his career in accounting and expand his experience in research-related accounting managed by well-established systems and processes, he believes that MCRI is the ideal place for his professional growth.