Clinical trial NCT02961465: Effectiveness and Safety of Sacral Neuromodulation in Patients With Idiopathic Slow-transit Constipation
Official title: Effectiveness and Safety of Sacral Neuromodulation in Patients With Idiopathic Slow-transit Constipation Refractory to Conservative Treatments
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Constipation
Surgery
Keywords: Sacral neuromodulation
Constipation
Slow-transit constipation
Surgery
Colorectal surgery
Cost-effectiveness
Quality of life
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch National Health Care Institute
name: Medtronic
First posted: 2016-11-11
Enrollment: 23
Sex: ALL
Minimum age (years): 14
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population consists of adolescents (14-17 years) and adults (18-80 years) with idiopathic slow-transit constipation refractory to conservative treatment. As data regarding this population is limited it is virtually impossible to provide precise numbers of this patient population. However, some numbers are known:

* Average prevalences of idiopathic constipation of 16% and 19.2% are reported in Europe
* Of all patients treated for constipation, 5.6% is treated at the hospital
* It is estimated that 1% of the constipation patients who are treated with conservative treatment in hospitals, are unresponsive and are eligible for sacral neuromodulation
* Over the last 6 years, annually, on average, 25 patients were treated with SNM at the Maastricht UMC+ and the Groene Hart Ziekenhuis Gouda

Brief summary: Rationale: Previous reviews showed that the evidence regarding the effectiveness of sacral neuromodulation (SNM) in patients with therapy-resistant, idiopathic (slow-transit) constipation is of suboptimal quality. Furthermore, there is no estimate of costs and cost-effectiveness in this patient group.

Study design: A prospective cohort study with one group. This study is conducted next to a randomized controlled clinical trial (RCT) on 'the effectiveness and cost-effectiveness of sacral neuromodulation in patients with idiopathic slow-transit constipation refractory to conservative treatments' (for more information ClinicalTrial.gov ID: NCT02961582). This RCT is part of a temporary reimbursement arrangement, called conditional reimbursement of health care (in Dutch: Voorwaardelijke Toelating) of the National Health Care Institute (Zorginstituut Nederland). As part of this arrangement, the Ministry of Health, Welfare and Sports requires that SNM remains available for eligible patients during the conditional reimbursement period, also when inclusion of the RCT has ended. Furthermore, the Ministry requires that patients who received personalized conservative treatment in the RCT (control group), are offered SNM after completion of their follow-up of 6 months. As a result, the National Health Care Institute requires that the patients who receive SNM outside the RCT are included in a prospective cohort study to be able to collect data on them.

Aim: The aim of this prospective cohort study is to collect more (but uncontrolled) information regarding the safety and effectiveness of SNM.

Study population: Adolescent (14-17 years) and adult (18-80 years) patients with idiopathic slow-transit constipation refractory to conservative treatment.

Intervention: The intervention is SNM, a minimally invasive surgical procedure consisting of two phases. In the screening phase an electrode is inserted near the third sacral nerve and connected to an external stimulator. If the screening phase is successful (average defecation frequency (DF) ≥3 a week), the electrode is connected to a pacemaker that is implanted in the buttocks of the patient. If not successful, the pacemaker will be removed and patients receive conservative treatment.

Main study parameters/endpoints: The primary outcome is treatment success at 6 months, defined as an average DF of ≥3 a week according to a 3-week defecation diary and safety. Secondary outcomes are straining, sense of incomplete evacuation, constipation severity and generic (health-related) quality of life ((HR)QOL).


Eligibility criteria: Inclusion Criteria:

* An average defecation frequency (DF) of \<3 per week based on a 3-week defecation diary (patient-reported)
* Meet at least one other criterion of the Rome-IV criteria for idiopathic constipation based on the 3-week defecation diary (1)
* Refractory to conservative treatment
* Age: 14-80 years
* Slow-transit constipation

  (1) Rome-IV criteria for idiopathic constipation:
* Straining during ≥25% of defecations
* Lumpy or hard stools in ≥25% of defecations
* Sensation of incomplete evacuation for ≥25% of defecations
* Sensation of anorectal obstruction/blockage for ≥25% of defecations
* Manual manoeuvres to facilitate ≥25% of defecations

Exclusion Criteria:

* Obstructed outlet syndrome (objectified by defeacography)
* Irritable bowel syndrome (Rome-IV criteria for irritable bowel syndrome)
* Congenital or organic bowel pathology
* Rectal prolapse
* Anatomical limitations preventing placement of an electrode
* Skin and perineal disease with risk of infection
* Previous large bowel/rectal surgery
* Stoma
* Coexisting neurological disease
* Significant psychological co-morbidity as assessed subjectively by the investigator
* Being or attempting to become pregnant during study follow-up

Primary outcomes:
measure: Treatment success at 6 months
timeFrame: 6 months
measure: Complications/adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of patients with a 50% reduction in the proportion of defecations with straining
timeFrame: Baseline, 1, 3 and 6 months, (12 months)
measure: Proportion of patients with a 50% reduction in the proportion of defecations with a sense of incomplete evacuation
timeFrame: Baseline, 1, 3 and 6 months, (12 months)
measure: Constipation severity
timeFrame: Baseline, 1, 3 and 6 months, (12 months)
measure: Generic (HR)QOL
timeFrame: Baseline, 1, 3 and 6 months, (12 months)
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
state: Zuid-Holland
Study officials:
affiliation: Maastricht University Medical Centre
name: Stéphanie O Breukink, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Centre
name: Carmen D Dirksen, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review. Best Pract Res Clin Gastroenterol. 2011 Feb;25(1):3-18. doi: 10.1016/j.bpg.2010.12.010.
citation: Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011 Sep;106(9):1582-91; quiz 1581, 1592. doi: 10.1038/ajg.2011.164. Epub 2011 May 24.
citation: van Wunnik BP, Peeters B, Govaert B, Nieman FH, Benninga MA, Baeten CG. Sacral neuromodulation therapy: a promising treatment for adolescents with refractory functional constipation. Dis Colon Rectum. 2012 Mar;55(3):278-85. doi: 10.1097/DCR.0b013e3182405c61.