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

• ClinicalTrials.gov Identifier: NCT02748590
• Recruitment Status: Completed
• First Posted: April 22, 2016
• Last Update Posted: April 1, 2020
• Sponsor: Nantes University Hospital
• Information provided by (Responsible Party): Nantes University Hospital

Tracking Information

• First Submitted Date: April 14, 2016
• First Posted Date: April 22, 2016
• Last Update Posted Date: April 1, 2020
• Study Start Date: June 2016
• Actual Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2016)

Efficacy of neuromodulation to induce remission at Week 8 in patients with moderate to severe active ulcerative colitis (Mayo score) [ Time Frame: 8 weeks ]

Clinical and endoscopic remission as measured by the Mayo score ≤ 2 points without any criteria> 1 point to week 8

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 25, 2016)

• Assess the Remission at Week 16 ( Mayo score) [ Time Frame: 16 weeks ]
  Remission is defined by a Mayo score ≤ 1 point.
• Assess the Response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  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.
• Assess the clinical response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  The answer Clinic is defined as a decrease of at least 3 points in the score Clinic dimension compared to baseline.
• Assess the endoscopic response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  Endoscopic response corresponds to a decrease of at least 1 point in the endoscopic score
• Assess the histological response at Week 8 and Week 16 (Geboes Score) [ Time Frame: 16 weeks ]
  Mucosal healing is defined by a score of Geboes less than or equal to 1 of the biopsy examination
• Assess the biological response at Week 8 and Week 16 (C-reactive protein) [ Time Frame: 16 weeks ]
  Biological response is defined as a decrease of C-reactive protein
• Assess the biological response at Week 8 and Week 16 (Calprotectin) [ Time Frame: 16 weeks ]
  Biological response is defined as a decrease of fecal calprotectin.
• Evaluate the symptom's resolution at Week 3, Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  The resolution is defined by bleeding Ulcerative Colitis Disease Activity Index sub-score 0
• Evaluate the urgencies cessation at Week 3, Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  The resolution is defined by bleeding Ulcerative Colitis Disease Activity Index sub-score 0
• Evaluate the cessation of rectal bleeding at Week 8, Week 16 [ Time Frame: 16 weeks ]
  Cessation of rectal bleeding is defined as rectal bleeding Ulcerative Colitis Disease Activity Index sub-score of 0
• Evaluate the immunosuppressive drugs at Week 8 and Week 16 [ Time Frame: 16 weeks ]
  Absence or decreasing in immunosuppressive drugs during the follow-up
• Evaluate the need for steroids at Week 8 and Week 16 [ Time Frame: 16 weeks ]
  The need for steroid treatment at least once during the follow-up period
• Evaluate the tolerance of neuromodulation in Ulcerative Colitis patients at Week 3, Week 8 and Week 16 [ Time Frame: 16 weeks ]
  Tolerance of neuromodulation is stated by symptom specific scale
• Evaluate the quality of life of the patients at Week 8 and Week 16 (Scale The Short Form 36) [ Time Frame: 16 weeks ]
  Quality of life is evaluated with The Short Form 36 scale
• Assess abdominal discomfort for weeks at Week 8 and Week 16 [ Time Frame: 16 weeks ]
  Bristol Stool Scale

Original Secondary Outcome Measures (submitted: April 21, 2016)

• Assess the Remission at Week 16 ( Mayo score) [ Time Frame: 16 weeks ]
  Remission is defined by a Mayo score ≤ 1 point.
• Assess the Response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  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.
• Assess the clinical response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  The answer Clinic is defined as a decrease of at least 3 points in the score Clinic dimension compared to baseline.
• Assess the endoscopic response at Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  Endoscopic response corresponds to a decrease of at least 1 point in the endoscopic score
• Assess the histological response at Week 8 and Week 16 (Geboes Score) [ Time Frame: 16 weeks ]
  Mucosal healing is defined by a score of Geboes less than or equal to 1 of the biopsy examination
• Assess the biological response at Week 8 and Week 16 (C-reactive protein) [ Time Frame: 16 weeks ]
  Biological response is defined as a decrease of C-reactive protein
• Assess the biological response at Week 8 and Week 16 (Calprotectin) [ Time Frame: 16 weeks ]
  Biological response is defined as a decrease of fecal calprotectin.
• Evaluate the symptom's resolution at Week 3, Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  The resolution is defined by bleeding Ulcerative Colitis Disease Activity Index sub-score 0
• Evaluate the urgencies cessation at Week 3, Week 8 and Week 16 (scale Ulcerative Colitis Disease Activity Index) [ Time Frame: 16 weeks ]
  The resolution is defined by bleeding Ulcerative Colitis Disease Activity Index sub-score 0
• Evaluate the cessation of rectal bleeding at Week 8, Week 16 [ Time Frame: 16 weeks ]
  Cessation of rectal bleeding is defined as rectal bleeding Ulcerative Colitis Disease Activity Index sub-score of 0
• Evaluate the immunosuppressive drugs at Week 8 and Week 16 [ Time Frame: 16 weeks ]
  Absence or decreasing in immunosuppressive drugs during the follow-up
• Evaluate the need for steroids at Week 8 and Week 16 [ Time Frame: 16 weeks ]
  The need for steroid treatment at least once during the follow-up period
• Evaluate the tolerance of neuromodulation in Ulcerative Colitis patients at Week 3, Week 8 and Week 16 [ Time Frame: 16 weeks ]
  Tolerance of neuromodulation is stated by symptom specific scale
• Evaluate the quality of life of the patients at Week 8 and Week 16 (Scale The Short Form 36) [ Time Frame: 16 weeks ]
  Quality of life is evaluated with The Short Form 36 scale
• Assess pain and abdominal discomfort for weeks at Week 8 and Week 1 [ Time Frame: 16 weeks ]
  Bristol Stool Scale

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Sacral Neuromodulation (SNM) in the Treatment of Active Ulcerative Colitis (PRIMICISTIM)
• Official Title: Evaluation of Sacral Neuromodulation (SNM) in the Treatment of Active Ulcerative Colitis
• Brief Summary: Efficacy of ulcerative colitis to induce remission in patients with moderate to severe active ulcerative colitis.

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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Active Ulcerative Colitis

Intervention

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

Study Arms

Experimental: Neuromodulation

Intervention: Device: InterStim II Neurostimulator Model 3058

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 30, 2020): 8
• Original Estimated Enrollment (submitted: April 21, 2016): 12
• Actual Study Completion Date: January 2020
• Actual Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02748590
• Other Study ID Numbers: RC15_0448
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Nantes University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Nantes University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Nantes University Hospital
• Verification Date: March 2020