Clinical trial NCT01629303: Efficacy of Sacral Nerve Modulation in Severe Refractory Constipation
Official title: Efficacy of Sacral Nerve Modulation in Severe Refractory Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Constipation
Keywords: constipation
sacral nerve modulation
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2012-06-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Subjects with refractory chronic constipation are offered two conventional therapeutic strategies: either medical treatment, either surgery (in the case of medication failure). Nevertheless, a procedure less invasive than surgery could be an alternative strategy: the sacral nerve modulation. This procedure consists in stimulating the nerves which control the contractions of the colon and so the defecation phenomenon. Several open trials have suggested that sacral nerve modulation may be effective in reducing constipation and related symptoms. The aim of this randomized clinical trial is to assess the efficacy of the sacral nerve stimulation in patients with constipation.

Detailed description: The prevalence of constipation is 2-27% in Western countries. For patients failing medical treatment (laxatives, biofeedback), a surgical solution may be considered (subtotal colectomy). But results are variable and it puts them at risk of functional sequelae.

Sacral nerve modulation is a minimally invasive procedure compared with the standard surgical support (colectomy) and reversible, which consists in two stages. First, a 3-week temporary stimulation test allows verifying the efficacy of neuromodulation. If the test is positive, the stimulating electrode is definitely implanted. Risks related to the procedure (infection, pain) are much smaller than those associated with a conventional surgical support.

Non comparative studies conducted with 19 and 62 patients showed that 40-73% of implanted patients have an improvement of their constipation and could benefit of permanent implantation with good results in medium term.

The primary objective of the investigators study is to evaluate the short-term efficacy (percentage of responders at 2 months) of sacral nerve modulation in the treatment of severe chronic constipation.

This is a cross-over designed, double-blinded, French multicenter clinical trial, including two periods: 2 months of stimulation ON and 2 months of stimulation OFF. Between these two periods, a 15-days period of "wash-out" will be respected during which all patients will be in OFF mode (4.5 months in total). This period of 4.5 months will be extended by a follow-up period of 7 months during which all patients will be treated (stimulation ON).

If this trial showed efficiency of this procedure, patients with severe refractory constipation could benefit of a sacral nerve modulation test before considering a surgical treatment.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Constipation defined by at least two of the following criteria :

  * Frequency of 2 stools or less per week
  * Severe outlet constipation, i.e. need to use digital extraction or enemas more than 25% of time
  * Sensation of incomplete evacuation more than 25% of time
* Refractory constipation since at least 1 year to medical treatment (drug treatment and/or biofeedback) conducted in the centre (failure or intolerance to laxative osmotic treatments, stimulants, and prucalopride) for which surgery is discussed
* Patients supported in the centre for at least 3 months before inclusion
* Patients having social security system
* Patients having read and signed informed consent form

Exclusion Criteria:

* Constipation secondary to ano-rectal malformation, surgical sequel, colorectal or anal organic lesions, or pelvi-perineal static disorder indicated for surgical treatment
* Constipation secondary to neurological pathology and/or concomitant treatments intake (opiates, anticholinergic agents)
* Partial colectomy history
* Patients in whom implantation of stimulating electrode is impossible due to anatomical reasons (e.g. sacral agenesis)
* Pregnant female patients or with childbearing potential without adequate contraceptive barrier (oestrogen-progesterone contraceptives or intra-uterine device)
* Skin disease associated with a risk of infection - in the opinion of the investigator
* Patient with pacemaker or defibrillator
* Patient exposed to resonance magnetic imaging
* Psychiatric disease incompatible with use of the treatment - in the opinion of the investigator
* Patient misunderstanding oral and written French language
* Patient participating to another study
* Patients who don't complete the first diary without missing data (concerning items used to define the primary endpoint)

Primary outcomes:
measure: Percentage of patients showing a positive response to sacral nerve stimulation at 2 months
timeFrame: 2 months of the stimualtion period
Secondary outcomes:
measure: Clinical characteristics, manometry data, Wexner score of responders to stimulation during the temporary stimulation test (period before the permanent implantation)
timeFrame: 3 weeks between temporary and permanent implantations
measure: Clinical characteristics, manometry data, Wexner score of responders to short-term stimulation
timeFrame: 2 months after permanent implantation
measure: Efficacy of neuromodulation
timeFrame: 1 year after permanent implantation
measure: Manometry data, Wexner, QoL and EVA scores, time of colonic transit of responders to prolonged stimulation
timeFrame: 1 year after permanent implantation
measure: To evaluate the investigator opinion about the neuromodulation response, using the patient diary.
timeFrame: 1 year after permanent implantation
Other outcomes:
Locations:
city: CHU de Limoges
country: France
facility: Service d' Hépato-gastro-entérologie
state: Limoges
city: Bordeaux
country: France
facility: Service d'hépato-gastroentérologie et oncologie digestive
city: Clermont Ferrand
country: France
facility: Service d'hépato-gastroentérologie - CHU estaing
city: Colombes
country: France
facility: Service de gastroentérologie - AP HP
city: Grenoble
country: France
facility: Service de Chirurgie générale - CHU de Grenoble
city: Lyon
country: France
facility: Service d'exploration fonctionnelle digestive -Hospices Civils de Lyon
city: Marseille
country: France
facility: Service de gastroentérologie - hopital nord -AP-HM
city: Nantes
country: France
facility: : Clinique de chirurgie digestive et endocrinienne. Institut des Maladies de l'Appareil Digestif (IMAD
city: Rennes
country: France
facility: SMAD CHU Pontchaillou -Rennes
city: Rouen
country: France
facility: Service de physiologie digestive, urinaire, respiratoire et sportive - CHU de rouen
city: Tours
country: France
facility: Service d'hépato-gastroentérologie et explorations fonctionnelles digestives - CHU de Tours
Study officials:
affiliation: University Hospital, Bordeaux
name: Frank ZERBIB, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux
name: Genevieve CHENE, Professor
role: STUDY_CHAIR
References:
citation: Zerbib F, Siproudhis L, Lehur PA, Germain C, Mion F, Leroi AM, Coffin B, Le Sidaner A, Vitton V, Bouyssou-Cellier C, Chene G; CONSTIMOD study investigators. Randomized clinical trial of sacral nerve stimulation for refractory constipation. Br J Surg. 2017 Feb;104(3):205-213. doi: 10.1002/bjs.10326. Epub 2016 Oct 25.