Hypnotherapy for Prevention of Relapse in Ulcerative Colitis: a Randomised, Single-blind, Controlled Clinical Trial

Study Overview
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Brief Summary
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There is increasing evidence that worsening of ulcerative colitis (UC) can be provoked by psychological stresses. When this protocol was devised, there had been no proper scientific studies to find out whether stress reduction can improve the course of UC. Hypnotherapy is a technique by which a practitioner induces a temporary trance-like state in patients: while they are in this state, the practitioner uses suggestion to induce relaxation as well as beneficial modification of the way in which the patient experiences the gut working. In previous studies in our lab, we have shown that a single 50 minute session of hypnosis can reduce special indicators of inflammation both in the blood-stream and in the lining of the lower bowel (rectum). Furthermore, in earlier work by others, hypnosis had been shown to be effective in the treatment of patients with irritable bowel syndrome, duodenal ulcer and indigestion unassociated with ulcers. Many patients with UC need to take the immunosuppressive drug, azathioprine, in addition to a 5ASA drug, to keep their disease under control. While azathioprine is usually effective in maintaining remission of UC, it does require regular drug checks and carries the risk of possible side-effects. We undertook a study of hypnotherapy to see whether it can prevent relapse (worsening) of UC in patients who normally need to take azathioprine to keep their UC inactive. To do this, we planned to ask 66 patients who agreed to participate in the trial to stop their azathioprine. They were then to be allocated to receive either gut-focussed hypnotherapy (44 patients) or, as a control, non-emotive educational sessions (22 patients) once a month for 3 months, with intervening self-hypnosis daily in the active arm. The numbers of patients in each group who developed relapse of their UC in a year were recorded. We diagnosed relapse from patients' diaries recording diarrhoea and bleeding, and by sigmoidoscopy. It was hoped that this clinical trial would identify a new drug-free way of reducing the chances of relapse in patients with UC.

Detailed Description
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SCIENTIFIC ABSTRACT There is increasing evidence that relapse of ulcerative colitis (UC) can be provoked by psychological stress. When this study was planned, there were no proper scientific studies to find out whether stress reduction can improve the course of UC. Hypnotherapy is a technique by which a practitioner induces a temporary trance-like state in patients: while they are in this state, the practitioner uses suggestion to induce relaxation as well as beneficial modification of the way in which the patient experiences the gut working. In previous studies in our lab, we had shown that a single session of hypnosis can reduce measures of inflammation at both systemic and rectal mucosal levels. Thus, 50 min of gut-focussed hypnosis reduced serum interleukin-6 (IL6) and non-killer (NK) cell numbers in circulating blood, as well as rectal mucosal release of interleukin-13 (IL13), substance P and histamine. Furthermore, in earlier work by others, hypnosis had been shown to be effective in the treatment of patients with irritable bowel syndrome, duodenal ulcer and indigestion unassociated with ulcers. Many patients with UC need to take the immunosuppressive, azathioprine, in addition to a 5ASA, to keep their disease in remission. While azathioprine is usually effective in maintaining remission of UC, it does require regular drug checks and carries the risk of possible side-effects. We undertook a study of hypnotherapy to see whether it could prevent relapse of UC in patients who normally need to take azathioprine to keep their UC inactive. To do this, we planned to ask 66 patients who agreed to participate in the trial to stop their azathioprine. They were then to be allocated to receive either gut-focussed hypnotherapy (44 patients) or, as a control, non-emotive educational sessions (22 patients) once a month for 3 months, with intervening self-hypnosis daily in the active arm. We then recorded relapse rates in each group at 1 year. We diagnosed relapse from patients' diaries recording the Simple Clinical Activity Index, and by Baron score >1 at sigmoidoscopy. It was hoped that this clinical trial would identify a new drug-free way of reducing the chances of relapse in patients with UC withdrawing from treatment with azathioprine.

Official Title
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Hypnotherapy for Prevention of Relapse in Ulcerative Colitis: a Randomised, Single-blind, Controlled Clinical Trial

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Behavioral: Gut focussed hypnotherapy
* Behavioral: Control educational sessions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inactive UC Age 16-75 years Minimum 1 year on Azathioprine or Mercaptopurine. Simple Colitis Activity Index (SCCAI) score <3 Baron's sigmoidoscopic score <2 . In remission for at least 3 months No change to other maintenance therapy (including 5ASA) for at least 4 months Exclusion Criteria: Use of prednisolone orally or topically, or of topical 5ASA for at least 3 months Antibiotics, warfarin, anti-diarrhoeal drugs, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin > 75 mg/day Herbal remedies Alcohol or drug abuse Pregnancy or breast feeding Female of child-bearing age not taking adequate contraception Participation in another drug trial in the previous three months Serious liver, renal, cardiac, respiratory, endocrine, neurological or psychiatric illness Already use relaxation techniques or computerized feedback

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gut-focussed hypnotherapy (GFH).<br>Gut-focussed hypnotherapy (GFH). | Behavioral: Gut focussed hypnotherapy<br>* Gut focussed hypnotherapy<br>|
| Sham Comparator: Educational sessions<br>Regular sessions to learn about UC from research nurse | Behavioral: Control educational sessions<br>* Control educational sessions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse at 1 Year | The number of patients suffering a relapse was compared between the two treatment groups, and was the primary outcome parameter of this study. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 13 | IBDQ (standard measure of IBD patients' Quality of life (QoL) (Irvine et al 1982 approx). The IBDQ is a validated and reliable tool to measure of health-related quality of life in adult patients with IBD. The questionnaire consists of 32 questions scored in four domains: bowel symptoms, emotional health, systemic systems and social function. Scores range from 1 (poorest QoL) to 7 (best QoL). Higher scores indicate better QoL. Lowest score 7, highest score 224. | 13 weeks | 
| Hospital Anxiety and Depression Score-Anxiety, (HADSA) at Week 13 | Measure of anxiety, HADS Hospital anxiety and depression scale. HADS questionnaire consists of a 14 question validated questionnaire, developed to measure anxiety and depression in the hospital setting. Each item is answered by the patient on a four point (0-3) response category so the possible scores range from 0 (minimum) to 21 (maximum) for anxiety and 0 (minimum) to 21 (maximum) for depression. Higher scores indicate worse outcome, | 13 weeks | 
| Hospital Anxiety and Depression Score-Depression (HADSD) | Measure of depression. Each item is answered by the patient on a four point (0-3) response category so the possible scores range from 0 to 21 for anxiety and 0 to 21 for depression. Each item is answered by the patient on a four point (0-3) response category so the possible scores range from 0 (minimum) to 21 (maximum) for anxiety and (minimum) to 21 (maximum) for depression. Higher scores worse outcome. | 13 weeks | 
| Perceived Stress Questionnaire-Recent (PSQ-R) | Measure of recent psychological stress. THE PSQ R consists of a 30 question questionnaires: recent, in which the statements used apply to the last month in which used statements apply to the last two years (Appendix 1.3). The score for both recent and general stress levels were stated as the PSQ index ranging from 0 (non-stressed) to 0.99 (highly stressed). Higher scores indicate worse outcome. | 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypnotherapy, Prevention of relapse, ulcerative colitis