Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03812094 |
| Other study ID # |
BAAT-01 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2019 |
| Est. completion date |
June 1, 2021 |
Study information
| Verified date |
December 2021 |
| Source |
Dalarna County Council, Sweden |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Enuresis is the scientific term for bedwetting. Modern research has established three
pathogenic mechanisms as crucial:
1. Excessive urine production at night (nocturnal polyuria).
2. Detrusor over activity. The bladder may contract regardless of whether it is full or
not.
3. Difficulties to arouse from sleep and will not wake up when the bladder is full or
contracts.
Children with daytime incontinence usually suffer from detrusor over activity and many of
them are constipated. The reason for this connection is probably partly anatomical;
constipated children have to use the rectum as a storage space, and the chronically distended
rectum will compress the bladder from behind.
The link between constipation and enuresis (as opposed to daytime incontinence) is less clear
although it is logically plausible. Our experience is that some enuretic children become dry
at night just by treatment of constipation, but this is yet not supported by sufficient
evidence The standard primary treatment of enuresis - as reflected by global consensus
guidelines - rests upon three pillars. The recommended first step is 1) bladder advice. The
next step, if the child is still wet at night, is either 2) the antidiuretic drug
desmopressin or 3) the sleep-modifying enuresis alarm.
The underlying idea behind basic bladder advice is that the child is taught to more actively
take command over the bladder by voiding according to a regular daytime schedule, using
correct voiding posture and spread fluid intake evenly across the day. The rationale behind
the recommendation of this strategy is that is the established cornerstone of the treatment
of daytime incontinence and that detrusor over activity is a pathogenic factor common to both
conditions. By influencing bladder, function during the day it is assumed that nocturnal
bladder function will also normalize. The problem is a glaring lack of evidence.
Our primary aims with this study is to better understand which roles basic bladder advice,
constipation therapy and/or the enuresis alarm play in the first-line therapy of enuresis.
Description:
Treatment strategies in nocturnal enuresis
BACKGROUND. Enuresis is the scientific term for bedwetting. Approximately one in ten children
in early school age suffers from this condition. Modern research has established three
pathogenic mechanisms as crucial:
1. Excessive urine production at night (nocturnal polyuria). The bladder is filled to
capacity before the night is over.
2. Nocturnal detrusor overactivity. In these cases, the bladder may contract regardless of
whether it is full or not.
3. Almost all children with enuresis are difficult to arouse from sleep and will not wake
up when the bladder is full or contracts.
Regardless of which of the above factors is relevant in the individual child, the condition
is often inherited.
All enuretic children do not wet their beds every night, but even children who experience wet
nights sporadically may be very much bothered by their condition - they may, for instance,
not dare to participate in school camps or sleepovers. Many of the children also suffer from
concomitant daytime incontinence.
Enuresis is not, as previously thought, primarily a psychiatric disorder. It has psychiatric
consequences, but only rarely psychiatric causes. Enuretic children, as group, have lower
self-esteem than their dry peers, and their quality of life is also negatively affected.
Another link between the bladder and the psychological wellbeing of the child is that, for
unclear reasons, enuresis (as well as daytime incontinence) is overrepresented among children
with neuropsychiatric disturbances such as ADHD, and vice versa. These considerations make
the successful treatment of enuresis extra important.
THE BLADDER-BOWEL LINK. It is well established that children with daytime incontinence
usually suffer from underlying detrusor overactivity and that many of them are constipated.
Treatment of daytime incontinence in these children will usually only be successful if the
constipation is also treated. The reason for this connection is probably partly anatomical;
constipated children have to use the rectum as a storage space, and the chronically distended
rectum will compress the bladder from behind.
The link between constipation and enuresis (as opposed to daytime incontinence) is less clear
although it is logically plausible. Our experience is that some enuretic children become dry
at night just by treatment of constipation, but this is as yet not supported by sufficient
evidence. We neither know how common constipation is among enuretic children, nor how
important this, when present, is to treat.
CLINICAL EVALUATION OF THE ENURETIC CHILD. Children who seek medical attention for
uncomplicated enuresis usually do not need any complicated or invasive evaluation. No blood
samples need to be taken and no radiological or urodynamic examinations are motivated. A
nurse with a basic knowledge of pediatric bladder problems best evaluates children. If you
know how to ask, the right questions the very few children with enuresis due to serious
underlying conditions will easily be found.
The bladder diary plays a crucial role in the evaluation of children with bladder problems.
By writing down how often and how much urine the child voids during a few days, and by
assessing nocturnal urine production via the weighing of diapers or sheet covers, important
information is gained regarding bladder and kidney function during day and night. Additional
relevant information is provided if the family documents wet and dry nights, as well as bowel
movements, during two weeks.
TREATMENT. The standard primary treatment of enuresis - as reflected by global consensus
guidelines - rests upon three pillars. The recommended first step is 1) bladder advice, or
basic bladder advice. The next step, if the child is still wet at night, is either 2) the
antidiuretic drug desmopressin or 3) the sleep-modifying enuresis alarm.
The underlying idea behind basic bladder advice is that the child is taught to take command
over the bladder by voiding according to a regular day-time schedule, using correct voiding
posture and spread fluid intake evenly across the day. The rationale behind the
recommendation of this strategy is that is the established cornerstone of the treatment of
daytime incontinence and that detrusor over activity is a pathogenic factor common to both
conditions. By influencing bladder function during the day it is assumed that nocturnal
bladder function will also normalize.
The problem is a glaring lack of evidence. We do not know that daytime bladder training has
any influence at all on nocturnal enuresis. And the therapy, although completely harmless,
demands lots of nursing time and family commitment. We recently performed the first ever
randomised, controlled study of basic bladder advice in enuretic children and found no
effect. However, these results need to be further explored and confirmed before we know if
the global recommendations should be changed. Furthermore, during our completed study the
therapy was given during four weeks only and all participating children suffered from
frequent enuresis (i.e. enuresis occurring >50% of the nights). Thus, we still do not know
whether the treatment will help if it is given during a longer period or if children with
infrequent enuresis do have a beneficent effect of the therapy.
Desmopressin is taken at bedtime and, being an analogue to human vasopressin, decreases
nocturnal urine production. It helps 30-50% of enuretic children to achieve dry nights as
long as it is taken but has only limited, if any, curative effect.
The enuresis alarm is a device that gives off a strong alarm signal every time there is urine
in the bed. The method is well-established and has a clearly curative effect in more than
half of the children who use it, even though the therapeutic mechanism is slightly unclear.
Presumably, the use of the alarm either influences sleep and arousal mechanisms so the child
wakes up to void or learns to semi consciously inhibit nocturnal detrusor contractions; in
both cases, the enuresis disappears. The main problem with the alarm is that it demands a
high degree of motivation and compliance by the child and it may take months until full
effect is achieved.
In spite of these strategies, many enuretic children, perhaps 25%, are therapy-resistant. For
these children, who have experienced only failures, the burden and associated psychosocial
risks are extra high.
PROGNOSTIC INDICATORS Since different enuretic children have different causes behind their
bedwetting they will also respond differently to therapies. Much would be won if we could
choose correct therapy for the individual child at the first try.
It is known that desmopressin is likely (although not certain) to be beneficial if the
bladder diary shows that the nocturnal urine production is high and the daytime voided
volumes (volumes per micturition) are normal. However, prognostic indicators for alarm
response are much less studied - which is frustrating, given the high amount of work required
for this therapy.
We may presume that family motivation and the ability to follow instructions are
prognostically favourable indicators, but this assumption has never been properly tested.
There are some studies indicating that the alarm works best for children with frequent
enuresis but it is unclear whether factors such as nocturnal urine production, daytime
micturition habits, or indeed anamnestic data, give any prognostic information.
From the above background, it is clear that there are several questions that need to be
answered if a better, individualized and cost-effective enuresis therapy is to be achieved.
PRIMARY AIMS To better understand which roles basic bladder advise, constipation therapy
and/or the enuresis alarm play in the first-line therapy of enuresis.
SECONDARY AIMS
- Is constipation more common among enuretic children than normal controls?
- In enuretic children with constipation, how large effect against the enuresis has
treatment of the constipation?
- Do easily acquired data from the bladder diary give prognostic information as regarding
the antienuretic effect of basic bladder training and/or the alarm?
- Do children with infrequent enuresis respond differently to therapy than those who wet
their beds most nights?
- Which therapy is perceived as most cumbersome for the families - basic bladder advice or
the enuresis alarm? METHODS PROJECT I - ENURESIS AND CONSTIPATION. All patients and
controls visit the study nurse. They are asked a number of questions concerning bladder
and bowel habits and undergo non-invasive urodynamic examination, i.e. they empty their
bladder on the uroflow toilet and have any residual urine (urine left in the bladder
after voiding) detected via ultrasound. Ultrasound is also used to assess the diameter
of the rectum just behind the bladder. These procedures are all part of the routine
evaluation of children with bladder issues and involve no violation of privacy.
The nurse then supplies the family with a bladder diary, which is to be completed at home.
The following data is gathered:
- Wet and dry nights during two weeks (only patients)
- Nycturia (awake voiding's at night) during two weeks
- Voided volumes at each voiding during two days
- Fluid intake during two days and nights
- Weighing of diapers or sheet covers during three nights (only patients)
- Bowel movements during two weeks In addition to this the nurse notes the completeness of
the data and how long it takes for the family to return the bladder diary; i.e. the
family's motivation and ability to comply with the instructions is also assessed.
Enuretic children who have shown signs/symptoms of constipation (infrequent bowel movements,
faecal incontinence or a rectal diameter >30 mm) will be given standard laxative therapy and
their enuresis will be reassessed.
PROJECT II - RANDOMIZED COMPARISON BETWEEN BASIC UROTHERAPY, THE ENURESIS ALARM AND NO
TREATMET All enuretic children who completed project I and still suffer from enuresis -
including those who have been given treatment for constipation but did not become dry - will
be invited to take part in the randomised study. The participants will be randomised into
three groups. Regardless of group all children will be given information about bladder
function and enuresis pathogenesis, and all ongoing laxative therapy will continue.
The children will be randomized in to tree groups, "basic bladder advise", "alarm" or "no
treatment".
- Group A. Basic bladder advice is given in accordance with international guidelines. A
qualified pediatric nurse/ urotherapist give the treatment during 8 weeks. Contact by
phone is given in week 2 and 6. During the last two weeks (week 7 and 8) wet and dry
nights are again documented. At the end of treatment the family grades the level of
workload and disruption that the treatment has incurred.
- Group B. Alarm therapy according to international guidelines. Contact by phone is given
after in week 2 and 6. During the last two weeks (week 7 and 8) wet and dry nights are
again documented. At the end of treatment the family grades the level of workload and
disruption that the treatment has incurred.
- Group C. These children are given no active treatment. During the last two week, 7 and 8
wet and dry nights are again documented.
Regardless of which therapy has been given (or not given) the children who still wet their
beds after completion of project II will be given an appointment to the pediatric outpatient
ward for further treatment.
IMPLICATIONS AND RELEVANCE Through the results of this project we believe that first-line
treatment for a very large number of enuretic children will be improved, simplified and
rationalized. The impact will be international and global treatment recommendations may be
changed.
