Ulcerative Colitis
Conditions
Keywords
Hypnotherapy, Prevention of relapse, ulcerative colitis
Brief summary
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
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.
Interventions
BEHAVIORALControl educational sessions
Control educational sessions
BEHAVIORALGut focussed hypnotherapy
Gut focussed hypnotherapy
Sponsors
Barts & The London NHS Trust
Queen Mary University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse at 1 Year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 13 | 13 weeks | 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. |
| Hospital Anxiety and Depression Score-Anxiety, (HADSA) at Week 13 | 13 weeks | 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, |
| Hospital Anxiety and Depression Score-Depression (HADSD) | 13 weeks | 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. |
| Perceived Stress Questionnaire-Recent (PSQ-R) | 13 weeks | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
We aimed to recruit 66 patients from across London, but after \>3 years could recruit only 26. Reasons for failure to complete recruitment included the relative rarity of this patient-group (ie with inactive ulcerative colitis (UC) for some years while on thiopurine, willing to stop the drug, and with time to complete the intensive programme).
Participants by arm
| Arm | Count |
|---|---|
| Gut-focussed Hypnotherapy 16 Patients with inactive ulcerative colitis given gut-focussed hypnotherapy | 16 |
| Controlled Educational Sessions 10 Patients with inactive ulcerative colitis given educational sessions | 10 |
| Total | 26 |
Baseline characteristics
| Characteristic | Gut-focussed Hypnotherapy | Controlled Educational Sessions | Total |
|---|---|---|---|
| Age, Continuous | 31 years | 48 years | 35 years |
| Region of Enrollment United Kingdom | 16 participants | 10 participants | 26 participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 10 |
| other Total, other adverse events | 0 / 16 | 0 / 10 |
| serious Total, serious adverse events | 0 / 16 | 0 / 10 |
Outcome results
Primary
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.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| UC Patients Given Gut-focussed Hypnotherapy | Relapse at 1 Year | 8 Participants |
| UC Patients Given Control Educational Sessions | Relapse at 1 Year | 7 Participants |
Secondary
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,
Time frame: 13 weeks
Population: 4 hypnotherapy and 1 control patient failed to complete their questionnaires
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UC Patients Given Gut-focussed Hypnotherapy | Hospital Anxiety and Depression Score-Anxiety, (HADSA) at Week 13 | 7 score on a scale |
| UC Patients Given Control Educational Sessions | Hospital Anxiety and Depression Score-Anxiety, (HADSA) at Week 13 | 10 score on a scale |
Secondary
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.
Time frame: 13 weeks
Population: 4 hypnotherapy and 1 control patient failed to complete their questionnaires
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UC Patients Given Gut-focussed Hypnotherapy | Hospital Anxiety and Depression Score-Depression (HADSD) | 1.5 units on a scale |
| UC Patients Given Control Educational Sessions | Hospital Anxiety and Depression Score-Depression (HADSD) | 4 units on a scale |
Secondary
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.
Time frame: 13 weeks
Population: Patients all assessed at 13 weeks (end of treatment phase). 4 hypnotherapy and 1 control patient failed to complete their questionnaires
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UC Patients Given Gut-focussed Hypnotherapy | Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 13 | 195 units on a scale |
| UC Patients Given Control Educational Sessions | Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 13 | 192 units on a scale |
Secondary
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.
Time frame: 13 weeks
Population: 4 hypnotherapy and 1 control patient failed to complete their questionnaires
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UC Patients Given Gut-focussed Hypnotherapy | Perceived Stress Questionnaire-Recent (PSQ-R) | 0.3 units on a scale |
| UC Patients Given Control Educational Sessions | Perceived Stress Questionnaire-Recent (PSQ-R) | 0.4 units on a scale |