Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01157741 |
| Other study ID # |
2003-033 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
July 6, 2010 |
| Last updated |
July 7, 2010 |
| Start date |
October 2003 |
| Est. completion date |
June 2008 |
Study information
| Verified date |
December 2003 |
| Source |
International Centre for Diarrhoeal Disease Research, Bangladesh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Bangladesh: Ethical Review Committee |
| Study type |
Interventional
|
Clinical Trial Summary
Improved methods of community/home management and follow-up of severely undernourished
children need to be developed in low-income countries like Bangladesh. The proposed study
will be conducted at ICDDR,B Hospital and in different urban primary health care centres
within Dhaka city. The efficacy of four different interventions will be evaluated/compared
with control with respect to the rate of completion of clinical follow-up and growth,
morbidity, and changes in psychomotor development in 500 children aged 6-24 months
presenting to ICDDR,B with initial weight-for-age (WA) <-3 Z score. The interventions are:
1. Usual follow-up (fortnightly for 1st 3 months) service at the hospital nutrition
follow-up unit (HNFU) including growth monitoring and promotion + health education +
micronutrient supplementation and treatment of intercurrent illness (current standard
practice; control group).
2. All management like control group, but follow up at community-based nutrition follow-up
unit (CNFU) (fortnightly for 1st 3 months) (intervention A).
3. All management like intervention A at CNFU + supplementary food (SF) for the first 3
months (intervention B).
4. All management like intervention A at CNFU + psychosocial stimulation (PS) for the
first 3 months (intervention C).
5. All management like intervention A at CNFU + SF + PS for the first 3 months
(intervention D).
After the initial three months intervention period, children in all groups will be followed
on fortnightly basis for next three months in their respective follow up unit.
Follow-up rate, nutritional status, mental and psychomotor development, behavior,
morbidities (including intestinal permeability in a sub-sample) of the children, and child
rearing practices, depression and self esteem of mothers will be assessed in different
groups.
By ascertaining the most cost-effective/best management package, and by extending the
package to other systems in the country, it will be possible to rehabilitate a greater
number of severely malnourished children in their communities.
Description:
Study Design. A prospective, randomized, intervention trial.
Study site. The study will be conducted in Dhaka, Bangladesh. The children will be recruited
on discharge from the Dhaka Hospital of ICDDR,B after treatment of their acute illnesses,
and the follow up visits will be conducted at HNFU or CMFU (will be established) at four PHC
or community clinics of Demra, Gulshan, Sabujbagh and Mirpur thanas of Dhaka city. The
rationale for choosing these four thanas is that higher proportions of children with severe
malnutrition come from these four thanas or nearby areas (unpublished data; Ahmed et al.,
ICDDR,B, 2001).
Initial hospital-based treatment protocol. At ICDDRB, severely malnourished children are
treated in either the general ward or the special care unit of the Dhaka Hospital, according
to a standardized protocol [50], which is similar to that recommended by WHO [5].
Implementation of this protocol has resulted in a 47% reduction in the case-fatality rate
(CFR) among severely malnourished children [51] and according to recent observation there
was further reduction of the case-fatality rate to 68 % (the current CFR is 5.4%).
Criteria for enrollment. Once the children complete the initial phase of management of any
acute problems associated with severe malnutrition, they will be considered for recruitment,
according to the following inclusion criteria:
1. Age 6 - 24 months
2. Either sex
3. Severely malnourished [weight for age (WA) < -3 Z score]
4. Resolution of acute illnesses
5. Not planning to leave the current residence within next six months (for the purpose of
follow-up)
6. Informed consent granted from the guardian.
Exclusion Criteria. Children with any of the following clinical problems or other
limitations will be excluded from study:
1. Persistent anorexia, fever, severe wasting (WH < -3 Z score) or edema
2. Clinically apparent congenital/acquired disorders that may affect growth
3. Other acute or chronic diseases requiring hospitalization and/or affecting growth
4. Lack of fixed address (to avoid difficulties in tracing for follow up examinations)
5. Caregiver's condition: children accompanied by caregivers who are not able to give any
time for child care or unable to give stimulation due to any condition e.g. old age,
disease, physical or mental handicap.
Randomization. Once the children fulfill all the criteria for entry into the study and
written consent to participate is granted by their parents/guardian, the children will be
randomly assigned to one of the five treatment packages (control or interventions A, B, C or
D). Four sets of randomization will be done separately (one set each for the children coming
from four thanas- Demra, Gulshan, Sabujbagh and Mirpur or respective nearby thanas)
according to computer-generated random numbers using permuted blocks of block lengths of
five and ten. The assigned treatment packages will be kept in closed opaque envelopes until
the same serial number is assigned to an enrolled child.
Intervention: On the day of recruitment (i.e., on the day of discharge from the ICDDR,B
hospital after completion of acute phase management) a health worker (HW) will accompany the
child and mother to their home for identification of the home for any future home visits if
required, and next day the HW and a research assistant will go to the home to collect the
data about the quality of stimulation at home. At the beginning of the study, the importance
of bringing the child for clinical/nutritional follow up at the follow up unit (HNFU or CNFU
as assigned) at set intervals (according to assignment) after enrollment will be explained
to the mothers/caregivers. Among all scheduled follow-up visits, two visits i.e. at the end
of third and sixth month will be at HNFU and mothers/caregivers of all groups will be
advised to bring their children to HNFU during these two visits. The specific components of
treatment packages are described in the following sections.
Standard therapy: Standard therapy includes growth monitoring, health education, multiple
micronutrient supplementation, and clinical check up. In addition, self-referral will be
encouraged and entertained at any hour and day for intercurrent illnesses; children with
suspected serious illness, (e.g. dehydrating diarrhea, pneumonia, ear or throat infection,
fever, loss of appetite) will be admitted to the hospital, where standard treatment will be
provided.
Growth monitoring and promotion: During each follow up visit, the children's nutritional
status and general condition will be assessed. Anthropometrics will include weight,
length/height, mid-upper arm and head circumference, and the measures will be recorded on a
standardized form. The health workers will discuss child's overall condition, change in
weight and height and diet with respective mothers/caretakers.
Health education of mothers/caregivers: The major components of the process of education are
providing information, showing examples, practicing and checking understanding. During each
follow-up, mothers or caregivers will be given structured lessons (standardized previously)
by health worker on the causes and prevention of malnutrition, the importance of breast
feeding, preparation of nutritious low-cost diets with locally available food items, home
management of diarrhea, recognition of referral sign/symptoms of common illnesses, such as
pneumonia, and when to seek help, use of safe water and hygienic practices, and counseling
on birth spacing.
Micronutrient Supplementation. On recruitment and at each follow up visit during the first
three moths of the study, multivitamin drops, folic acid (in iron tablet) and zinc (standard
practice of ICDDR,B) will be provided for oral administration. Iron will be provided during
weeks 2-12 at a dose of 3 mg of elemental iron/kg/d. Caregivers will be asked to bring back
any leftover micronutrient/medicine at the time of each follow up visit to check the
compliance.
Other services: Other components of the treatment package that will be offered to children
in all study groups include: immunization according to the Expanded Programme on
Immunization guidelines, deworming of children >1 year of age if such treatment has not been
provided in the last six months, and counseling of parents on birth-spacing and
contraceptives, which will be provided free of cost to the mothers. At the end of six
months, if any child still has a WH < 90% (<-1 Z score), he/she will be invited to continue
attending the nutrition follow up clinic (regular service component) of ICDDR,B.
Follow up at the community-based clinics: Available data of 2001 showed that a good
proportion (~ 70%) of under-5 severely malnourished children were coming from four thanas
(Demra, Gulshan, Sabujbagh and Mirpur) or nearby areas of Dhaka city. One CNFU will be
established at each of these thanas within an already functioning PHC or NGO clinic. One
health worker contracted for the study will conduct the CNFUs on specified times and days of
the week.
Provision of supplementary food (SF): Children assigned to treatment groups B and D will
additionally receive the SF packets for first three months of the study as take-home
supplementary food in addition to their usual meals. The SF packets will be distributed on
recruitment i.e. at the time of discharge from the hospital and at each follow up visit from
the CNFU to the respective groups. A sufficient supply of packets will be provided to ensure
1 and 2 packets/day for 6 -11 and 12-24 months old children respectively until the next
planned follow-up, which we consider will be effective based on our previous experience. The
composition of each packet of the SF is (based on supplements commonly available through a
national supplementary feeding program in rural areas): 1) toasted rice powder 20g; 2)
toasted lentil powder 10g; 3) molasses 5g; and 4) soy bean oil 3g, and total energy per
packet is ~ 150 kcal (~ 630 k joules) with 11% energy from protein.
The ingredients will be bought from the local market and prepared in the HNFU-kitchen. The
health workers will measure the appropriate amounts into polythene packets under the
guidance of a research assistant (rice powder and lentil powder in one compartment, and
molasses and soybean oil in two separate compartments of each packet). Previous testing
revealed that the locally packaged supplements are stable for at least two months.
Caregivers will be asked to offer each packet mixed with (not more than) 30 ml (~ 6
teaspoonfuls) of water, and bring back any leftover food and/or empty packets at the time of
each follow up visit to check the compliance. Under-five siblings of the index children will
also receive the SF (according to their age, as stated above) for the 1st three months (to
minimize sharing of SF assigned to the study subject). Mothers/caregivers of other treatment
groups will receive education about how to prepare the SF at home and be encouraged to give
it to their children.
Psychosocial stimulation (PS): The intervention program is comprised of child stimulation
and parental counseling, which will be conducted by female health workers trained on how to
give psychosocial stimulation to the children and parental counseling, how to attract the
groups of attending mothers/caregivers, how to interact with the children and attract them
to the play materials, etc.
Data collection: At the beginning of the study information will be sought on the families'
wealth, standard of housing, family structure and parental characteristics. At the time of
each follow-up visit the children will be evaluated with regard to physical growth
(anthropometry), morbidity from infections and cognitive development and behavior. The data
collection methods and timing of each assessment are described below.
Anthropometry: At baseline and each subsequent scheduled follow-up visit the health worker
will record the children's nude weight, using a digital scale (Seca, model-345) with 10g
precision, length using a calibrated length board, and head and mid upper-arm circumference
to the nearest mm (non-stretch insertion tape), and triceps skinfold thickness by Harpenden
calipers to nearest 0.2mm. All anthropometrics will be taken twice; if they vary, a third
measurement will be done, and the average of the nearest two measures will be recorded. The
visits at the end of three and six month will be held at HNFU and the anthropometric
measurement taken there.
Morbidity: At each follow-up, the health worker will record child's morbidity since the
previous visit on a pre-coded form. Diarrhea will be defined as the passage of three or more
watery or liquid stools per day. An episode will be considered new if at least two
diarrhea-free days intervene between the current and the previous episodes. Acute lower
respiratory infection/pneumonia will be defined if there is cough + rapid respiratory rate
(> 50/min for 6-12 months group and > 40/min for older than 12 months group). Fever will be
noted if the mother thinks that her child's temperature is elevated, and cough will be
registered if reported to result in at least some discomfort to the child. Although the
definitions are somewhat subjective, we are planning to accept these definitions considering
the constraints of the field situation. Children will be admitted to the hospital if they
have any serious illness requiring hospital-based treatment.
Lactulose:Mannitol test: The test will be done in a randomly selected sub-sample of 15
children from each of the four intervention groups (A, B, C and D). Four sets of
randomization will be done separately (one set each for the children receiving interventions
A, B, C and D). There will be 100 opaque envelopes with serial number for each intervention
group and indication of Lactulose:Mannitol test be mentioned inside the envelope randomly in
15 out of 100. Incase any mother refuses the immediate next mother in the same group will be
asked for the test. Three ml sugar solutions per kg body weight (each 3 ml containing 400 mg
Lactulose + 100 mg Mannitol + up to 3 ml water) will be ingested in the morning of the day
of enrolment. After 30 minutes, they will be allowed to consume their usual meal and breast
milk. A urine collection bag will be placed just before the children consume the test dose
of sugars, and all urine will be collected for the next 5 hours. Every time the child
voides, the urine volume will be measured and recorded. One drop of 20% (wt/vol)
chlorhexidine gluconate will be added to each sample to prevent bacterial growth, and
approximately 3 ml of the pooled urine sample will be stored at -20OC until analysis. The
same procedure will be done at the end of the 3 months when the children will come to HNFU
for their follow-up visit. Urinary Lactulose and Mannitol (L:M) concentrations will be
measured in the Clinical Biochemistry Lab of ICDDR,B using an automated enzyme assay [55,
56]. For the sake of comparison we will also collect L:M data from 20 non-malnourished
children (one time) in the same community.
Outcome Measures:
Main outcomes:
- Rate of follow up
- Rate of weight gain
- Urinary Lactulose: Mannitol (ratio)
Other outcomes:
- Psychomotor development and behavior
- Maternal depression and self esteem
- Child rearing practices of mothers/caregivers
- Morbidities: episodes and percent of time reported with diarrhea, pneumonia, fever,
cough, and other illnesses
- Changes in length or height, head circumference and mid upper arm circumference
- Mortality rate, % of children remaining <-3Z score for WA
