Evaluation of Sacral Neuromodulation (SNM) in the Treatment of Active Ulcerative Colitis (PRIMICISTIM) (PRIMICISTIM)

Evaluation of Sacral Neuromodulation (SNM) in the Treatment of Active Ulcerative Colitis

Efficacy of ulcerative colitis to induce remission in patients with moderate to severe active ulcerative colitis.

Study Overview

• Status: Completed
• Conditions: Active Ulcerative Colitis
• Intervention / Treatment: Device: InterStim II Neurostimulator Model 3058

Detailed Description

Neuromodulation is a validated option for the treatment of fecal incontinence. Safety of this original approach has been confirmed by several studies. New indications for this minimally-invasive procedure are actually under evaluation particularly in the fields of irritable bowel syndrome and chronic constipation with promising results. Its mechanism of action remains partially unknown and the target of neuromodulation is not limited to the anal sphincter but the whole colonic motility seems to be influenced by this therapeutic approach. Moreover, recent experimental studies have shown that neuromodulation was able to reinforce the intestinal epithelial barrier involved in the pathophysiology of ulcerative colitis.

Subsequently, preliminary results in human have shown improvement of inflammation in patients suffering from inflammatory bowel diseases. In fact, despite recent improvement in medical therapies in inflammatory bowel diseases and particularly in ulcerative colitis, several patients are suffering from disabling chronic active disease. In those cases of refractory diseases, the only alternative treatment is a pan-proctocolectomy and ileal pouch surgery. This approach is a curative option, but leads to a significant morbidity and frequent functional disorders in the long-term follow-up (permanent stoma in 7 to 10% of the cases). Moreover, in limited distal disease (left colon and rectum) the surgical option seems to be unadapted and many patients remain symptomatic and suffer chronic active disease.

The aim of this study will be to assess in a prospective pilot study the efficacy of ulcerative colitis in inducing the remission of chronic active ulcerative colitis limited to the left side of the colon and improving the quality of life of the patients.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44000
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Active Ulcerative Colitis diagnosed on criteria Lennard Jones (31) for at least 1 year
• > 18 yo
• E1 - E2 disease or extended to transverse colon but not beyond the hepatic flexure (endoscopic pictures)
• resistant to medical treatment: active after introduction for at least 8 weeks of maintenance treatment (immunosuppressive or anti-TNF)
• Activity score >5 and endoscopic score >2
• Absence of bacterial infection in progress (Clostridium difficile)
• Affiliated with a social protection scheme and had signed an informed consent

Exclusion Criteria:

• Severe forms requiring hospitalization an intravenous treatment or immediate surgery
• infectious colitis or proctitis
• Prednisone> 20 mg / d
• Contraindications to the use of neuromodulator
• Corticosteroid therapy by intravenous route
• Pregnant women
• Major Trust

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neuromodulation	Device: InterStim II Neurostimulator Model 3058; The neuromodulation will be carried out according to the usual protocol: Hospitalization for the establishment of percutaneous electrode in the operating room under general anesthesia with fluoroscopic control. The pacemaker startup will be performed within 12h after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of neuromodulation to induce remission at Week 8 in patients with moderate to severe active ulcerative colitis (Mayo score)	Clinical and endoscopic remission as measured by the Mayo score ≤ 2 points without any criteria> 1 point to week 8	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Remission at Week 16 ( Mayo score)	Remission is defined by a Mayo score ≤ 1 point.	16 weeks
Assess the Response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index)	The response is defined as a decrease of at least 1 point in the item assessment by the physician and at least 1 point from the 3 other items with no increase in the other dimensions of the score.	16 weeks
Assess the clinical response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index)	The answer Clinic is defined as a decrease of at least 3 points in the score Clinic dimension compared to baseline.	16 weeks
Assess the endoscopic response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index)	Endoscopic response corresponds to a decrease of at least 1 point in the endoscopic score	16 weeks
Assess the histological response at Week 8 and Week 16 (Geboes Score)	Mucosal healing is defined by a score of Geboes less than or equal to 1 of the biopsy examination	16 weeks
Assess the biological response at Week 8 and Week 16 (C-reactive protein)	Biological response is defined as a decrease of C-reactive protein	16 weeks
Assess the biological response at Week 8 and Week 16 (Calprotectin)	Biological response is defined as a decrease of fecal calprotectin.	16 weeks
Evaluate the symptom's resolution at Week 3, Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index)	The resolution is defined by bleeding Ulcerative Colitis Disease Activity Index sub-score 0	16 weeks
Evaluate the urgencies cessation at Week 3, Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index)	The resolution is defined by bleeding Ulcerative Colitis Disease Activity Index sub-score 0	16 weeks
Evaluate the cessation of rectal bleeding at Week 8, Week 16	Cessation of rectal bleeding is defined as rectal bleeding Ulcerative Colitis Disease Activity Index sub-score of 0	16 weeks
Evaluate the immunosuppressive drugs at Week 8 and Week 16	Absence or decreasing in immunosuppressive drugs during the follow-up	16 weeks
Evaluate the need for steroids at Week 8 and Week 16	The need for steroid treatment at least once during the follow-up period	16 weeks
Evaluate the tolerance of neuromodulation in Ulcerative Colitis patients at Week 3, Week 8 and Week 16	Tolerance of neuromodulation is stated by symptom specific scale	16 weeks
Evaluate the quality of life of the patients at Week 8 and Week 16 (Scale The Short Form 36)	Quality of life is evaluated with The Short Form 36 scale	16 weeks
Assess abdominal discomfort for weeks at Week 8 and Week 16	Bristol Stool Scale	16 weeks

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 21, 2016
• First Posted (Estimate): April 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 1, 2020
• Last Update Submitted That Met QC Criteria: March 30, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: RC15_0448