Efficacy of Sacral Nerve Modulation in Severe Refractory Constipation

Constipation Clinical Trial

— CONSTIMOD  

Official title:

Efficacy of Sacral Nerve Modulation in Severe Refractory Constipation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01629303
• Other study ID #: CHUBX 2011/23
• Status: Completed
• Phase: Phase 2
• First received: June 11, 2012
• Last updated: July 22, 2015
• Start date: June 2012
• Est. completion date: January 2015

Study information

• Verified date: July 2015
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2015
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Constipation

Intervention

Procedure:
• sacral nerve modulation
After the definitive implantation, stimulators are placed in position ON (arm on-off) or OFF (arm off-on) for the first arm and in position OFF for the second arm during 8 weeks. Then all the stimulators are switched OFF (both first and second arms) for 15 days. Finally stimulators are maintained in position OFF for the first arm and switched ON for the second arm during 8 weeks

Locations

Country	Name	City	State
France	Service d'hépato-gastroentérologie et oncologie digestive	Bordeaux
France	Service d' Hépato-gastro-entérologie	CHU de Limoges	Limoges
France	Service d'hépato-gastroentérologie - CHU estaing	Clermont Ferrand
France	Service de gastroentérologie - AP HP	Colombes
France	Service de Chirurgie générale - CHU de Grenoble	Grenoble
France	Service d'exploration fonctionnelle digestive -Hospices Civils de Lyon	Lyon
France	Service de gastroentérologie - hopital nord -AP-HM	Marseille
France	: Clinique de chirurgie digestive et endocrinienne. Institut des Maladies de l'Appareil Digestif (IMAD	Nantes
France	SMAD CHU Pontchaillou -Rennes	Rennes
France	Service de physiologie digestive, urinaire, respiratoire et sportive - CHU de rouen	Rouen
France	Service d'hépato-gastroentérologie et explorations fonctionnelles digestives - CHU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients showing a positive response to sacral nerve stimulation at 2 months	Percentage of patients showing a positive response to sacral nerve stimulation during the period " ON " compared with the period " OFF " based on an objective assessment of the number of feces and their characteristics	2 months of the stimualtion period	No
Secondary	Clinical characteristics, manometry data, Wexner score of responders to stimulation during the temporary stimulation test (period before the permanent implantation)		3 weeks between temporary and permanent implantations	No
Secondary	Clinical characteristics, manometry data, Wexner score of responders to short-term stimulation		2 months after permanent implantation	No
Secondary	Efficacy of neuromodulation	Efficacy of neuromodulation (percentage of positive responders) at 1 year	1 year after permanent implantation	No
Secondary	Manometry data, Wexner, QoL and EVA scores, time of colonic transit of responders to prolonged stimulation		1 year after permanent implantation	No
Secondary	To evaluate the investigator opinion about the neuromodulation response, using the patient diary.		1 year after permanent implantation	No