Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201505001104412 Date of Approval: 16/04/2015
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title AMAZE
Official scientific title Amino acids and / or multiple Micronutrients in Adult Zambians with environmental Enteropathy: effects on intestinal structure & function and host-microbiome interactions. A randomised placebo controlled trial.
Brief summary describing the background and objectives of the trial Stunting & developmental delay affects over 150 million children under the age of 5 in the developing world. These children suffer from significant lifelong physiological & economic disadvantages far in excess of growing to become short adults. Despite improvements in nutrition & infectious disease burden, the prevalence of stunting in sub-Saharan Africa is 40%, unchanged for over 20 years. Environmental enteropathy (EE) is a highly prevalent asymptomatic disorder affecting adults & children in the developing world which is now thought to underlie stunting. It is believed to result from recurrent exposure to gut pathogens, resulting in intestinal inflammation, increased gut permeability, bacterial translocation & systemic immune activation, and reduced absorptive area leading to malabsorption. The immunology & pathophysiology of EE remain poorly understood, and there are no effective treatments. There is increasing evidence that nutritional status influences immune function, which may therefore affect the disease processes underlying EE. Several micronutrients are known to have important immunological roles in the mucosal immune system, and amino acid (AA) signalling through the mechanistic target of rapamycin (mTOR) pathway appears to play a crucial role in lymphocyte differentiation & function. Of note, micronutrient and high quality protein deficiencies are common in populations with EE due to both poor diet & impaired absorption. We are conducting this Phase II trial to investigate the effects of MM & AA supplementation in Zambian adults with environmental enteropathy on small bowel histology & permeability; microbial translocation; mucosal mTOR activation & immune function; and microbiome-host interactions. Outcomes will be compared before & after supplementation, and between interventions (supplementation groups). Effects of HIV status & comparisons to affluent Zambians without environmental enteropathy will also be explored.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) AMAZE
Disease(s) or condition(s) being studied Environmental enteropathy
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 01/06/2015
Actual trial start date
Anticipated date of last follow up 31/03/2016
Actual Last follow-up date
Anticipated target sample size (number of participants) 128
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
007-11-14 University of Zambia Biomedical Research Ethics Committee (UNZABREC)
ReDA 010299 Joint Research Managment Office, Queen Mary University of London (Sponsor)
CT054 Zambia Medicines Regulatory Authority (ZAMRA)
ReDA 010299 Joint Research Managment Office, Queen Mary University of London (Sponsor)
007-11-14 University of Zambia Biomedical Research Ethics Committee (UNZABREC)
CT054 Zambia Medicines Regulatory Authority (ZAMRA)
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised 16-block randomisation by computer-generated algorithm Code held by off-site study statistician Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group MM Immunace (R) Original two tablets + 'amino acid' placebo once daily 16 weeks Multiple micronutrient supplementation + 'amino acid' placebo 25
Experimental Group AA+MM L-Glutamine 29.9g + L-Leucine 2.79g +L-Tryptophan 280mg + 2 Immunace (R) Original tablets once daily 16 weeks Amino acid and multiple micronutrient supplementation 25
Control Group P 'Amino acid' placebo + 2 'micronutrient' placebo tablets once daily 16 weeks Double placebo 25 Placebo
Experimental Group AA L-Glutamine 29.9g + L-Leucine 2.79g +L-Tryptophan 280mg + 2 'micronutrient' placebo tablets once daily 16 weeks Amino acid supplementation + 'micronutrient' placebo 25
Control Group Unaffected control Nil Nil Unaffected control group - for baseline comparisons only 28
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Intervention arms (environmental enteropathy participants): Age between 18 and 60 years Resident in B section, Misisi compound Able to give informed consent Unaffected control group: Age between 18 and 60 years Able to give informed consent Household has running water, plumbed indoor toilet and electricity Household owns a vehicle and television In full-time education or full-time employment Resident in Woodlands, Kabulonga, Leopard¿s Hill, Ibex Hill, Longacres, Kalundu or other affluent suburb Already referred for diagnostic upper GI endoscopy indicated as part of standard clinical care Pregnancy (by self-report) Breast feeding (by self-report) Antibiotic use within previous 4 weeks Regular NSAID use within previous 4 weeks Diarrhoea within previous 4 weeks Significant comorbidity precluding endoscopy with sedation Therapeutic anticoagulation or bleeding diathesis precluding endoscopic biopsies Unwilling to undergo HIV testing Untreated helminth infection BMI < 18 Unwilling to consent to long-term storage of samples Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 60 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 22/01/2015 University of Zambia Biomedical Research Ethics Committee (UNZABREC)
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus Lusaka PO Box 50110 Zambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 22/01/2015 University of Zambia Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus, PO Box 50110, Lusaka, Zambia Lusaka PO Box 50110 Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Change in intestinal structure (by confocal laser endomicroscopy score and morphometry) in HIV seronegative participants before and after supplementation, according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Primary Outcome Change in mucosal T cell mTOR activity in HIV seronegative participants before and after supplementation, according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Change in plasma markers of microbial translocation in HIV seronegative participants, before and after supplementation according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Change in tight junction structure (by immunohistochemistry) in HIV seronegative participants, before and after supplementation according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Change in metabonomic and microbiome profile in HIV seronegative participants, before and after supplementation according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Change in small intestinal absorption and permeability in HIV seronegative participants, before and after supplementation according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Change in anthropometry and body composition before and after supplementation according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Change in plasma amino acid and micronutrient levels in HIV seronegative participants before and after supplementation, according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Chang in mucosal antimicrobial peptide expression in HIV seronegative participants, before and after supplementation according to treatment allocation. Before and after supplementation period (0 and 16 weeks)
Secondary Outcome All primary and secondary outcomes will be assessed in HIV seropositive participants Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Assessment of interaction between AA and MM interventions Before and after supplementation period (0 and 16 weeks)
Secondary Outcome Differences in measured outcome variables between partticipants with and without environmental enteropathy (baseline comparisons). Pre-supplementation / baseline (week 0)
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Endoscopy Department, University Teaching Hospital Nationalist Road Lusaka Zambia
St Lawrence Clinic Misisi Lusaka Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
CORE Charity 3 St Andrews Place London NW1 4LB United Kingdom
Vitabiotics Ltd 1 Apsley Way London NW2 7HF United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Queen Mary University of London Joint Research Management Office (JRMO), Queen Mary Innovation Centre, Lower Ground Floor, 5 Walden Street London E1 2EF United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Jonathan Swann Department of Food and Nutritional Sciences, University of Reading, Whiteknights Reading RG6 6AH United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Paul Kelly m.p.kelly@qmul.ac.uk +442078822643/+442078827191 Centre for Immunobiology, Blizard Institute, Newark Street
City Postal code Country Position/Affiliation
London E1 2AT United Kingdom Professor of Tropical Gastroenterology
Role Name Email Phone Street address
Public Enquiries John Louis-Auguste j.l.auguste@qmul.ac.uk +442078827198/+442078827191 Centre for Immunobiology, Blizard Institute, Newark Street
City Postal code Country Position/Affiliation
London E1 2AT United Kingdom Clinical Research Fellow
Role Name Email Phone Street address
Scientific Enquiries Paul Kelly m.p.kelly@qmul.ac.uk +442078822643/+442078827191 Centre for Immunobiology, Blizard Institute, Newark Street
City Postal code Country Position/Affiliation
London E1 2AT United Kingdom Professor of Tropical Gastroenterology
REPORTING
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