IBS: Visceral Sensitivity in Women With BS and Sexual Dysfunction
Study Details
Study Description
Brief Summary
This study aims to compare visceral rectal sensitivity and quality of life of 40 Irritable Bowel Syndrome women, with (20) and without sexual dysfunction (20). Both Irritable Bowel Syndrome (IBS) and sexual dysfunction (SD), decrease quality of life (QOL) separately, and only recently we have shown that quality of life decreases even more with both diseases. Thus, there is clinical evidence to search for a biological marker that explains this cumulative effect. Investigators will determine IBS using the Rome IV criteria, SD through the Female Sexual Function Index (FSFI) while and QOL through the Short Form-36 and the IBS-QOL. Visceral sensitivity will be evaluated by a barostat study: A small bag connected to a computer is placed in the rectum. This computer will insufflate air increasing the volume and simultaneously record the pressure inside the rectum; therefore investigators can simulate what happens when the stool reaches the rectum. The patient reports the first sensation, gas sensation, need to defecate and even pain. For patient protection the pressure will never exceed 50 mmHg and/or if any amount of pain is reported. To assess the effect of food on this visceral sensitivity, it is performed in 2 stages, fasting and 30 minutes after a standardized meal. The protocol will be carried out through 3 visits. First patients will be recruited; the diagnosis of IBS, SD, quality of life will be established and basic laboratory tests will be schedule before next visit. Second visit will be on day 7 of the menstrual cycle when investigators will carry out the barostat study and determination of blood´s sex hormones. The last visit is for the second barostat study on day 21 of the menstrual cycle with sex hormones measurement. This protocol will compare: Rectal pressure and volume for tone, first sensation, gas sensation, desire to defecate and pain, measure during fasting and postprandial periods in day 7 and 21 (estrogenic and progesterone phase) of the menstrual cycle. Other variables include (age, marital status, disease history, SF-36, IBS-QOL, etc.). This study aims to find a biological marker to explain the low QOL observed in daily clinical practice. This approach will allow us a more effective diagnosis and perhaps the creation of more effective therapeutic approaches to treat these patients. In the long term, we expect to establish the foundations of a patient-centered medicine with shared decision more effective in the gut brain axis disorders.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain related to alterations in defecation. Although the diagnostic criteria used in various consensuses may mask its true prevalence and incidence, it is known that it suffers between 5 and 15% of the population and it is more than two times more frequent in women. Only 10% of patients seek medical attention and even so it represents between 25 and 50% of gastroenterological visits in the United States. In Mexico the frequency is similar to that reported in the world.
IBS does not have a specific biological marker, but it is known that there are multiple factors involved in its pathophysiology. However, alterations in the gut-brain (GBA) are considered the main mechanism in the generation of symptoms.
The GBA regulates homeostatic functions through a set of organs that form a bidirectional network that links both elements. The neural portion includes peripheral elements (enteric nervous system, ENS), related elements (pairs of spinal and cranial nerves) and central (superior brain nuclei).
The ENS (neurons in the intestinal wall, epithelial and endocrine elements, associated neurotransmitters, and visceral smooth muscle) is the third division of the autonomic nervous system.
Once sensory information is captured in peripheral receptors, the information travels by intrinsic innervation to generate local reflexes in the viscera (absorption, secretion, motility and sensitivity) or by extrinsic innervations of the vagus nerve and thoracolumbar sympathetic afferent pathways towards the spinal medulla.
The main route of afferent activation is through the prevertebral ganglia that carry the signal to the dorsal horns of the spinal cord that travel through the lateral spinothalamic tract that, through the thalamus; activates cortical areas of pain somatic location and by limbic areas for emotional evaluation. These changes in the brain connectome are diverse and it is an area in development.
This complex GBA relationship in IBS patients includes differences in sex, comorbidities, and quality of life (QOL). These differences include the activation of estrogen receptors distributed along the visceral pain pathways (ENS, spinal cord and brain centers) as they modulate the opening of ion channels, regulate the tachykinin receptor NK1 and induce substance release. Additionally, estrogens modulate visceral information in the CNS. Elevated estrogen in the amygdale, increase the sensomotor response to rectal distention in oophorectomized rats. There are also studies that suggest that estrogens may alter the expression of specific pain receptors such as the glucocorticoid receptor and involve the opioid system. Changes have been observed in brain structure and functional connectivity in women, as well as other sexual factors. There are multiple overlaps with other functional digestive diseases, non-digestive diseases, and psychological and psychiatric disorders.
These complex connections make us see the IBS as a multisystemic disorder with alterations in QOL and other comorbidities, such as sexual dysfunction (SD). Since 1987 it has been shown that up to 83% of patients with IBS have SD. In 1993 it was recognized that sexual abuse may be related to IBS and that it alters the perception of pain. In 1998, SD was positively associated with the severity of gastrointestinal symptoms. Patients with IBS have a greater number of problems of physical and psychological abuse, the symptoms are aggravated with menstruation and are related to hormonal changes.
On the other hand, patients with IBS have shown visceral hypersensitivity. The best method to determine visceral mechanical sensitivity is the barostat. Recently, it has been shown that there is a relationship between the severity of symptoms, quality of life, psychological stress, colonic transit and visceral hypersensitivity in patients with IBS. Patients with IBS and a history of severe physical/sexual abuse have visceral hyposensitivity. IBS presents a higher frequency of SD, as well as a deteriorated QOL and visceral hypersensitivity.
No studies with barostat and determination of QOL have been conducted in the same population of patients with IBS and SD, comparing them with patients with IBS and without SD.
Establishing the relationship between QOL, SD and possible visceral hypersensitivity will make it possible to characterize this population and thus be able to establish new therapeutic strategies.
General hypothesis: Women with IBS and SD have greater visceral rectal hypersensitivity than those without SD.
Primary objective: To evaluate the pattern of rectal visceral sensitivity in patients with IBS and SD and compare it with patients with IBS without SD.
Secondary: To assess the QOL in patients with IBS with and without SD. Universe: Women with IBS with and without sexual dysfunction, who are cared for in the Gastroenterology service of the General Hospital of Mexico.
Sample. Group 1: Patients with IBS and sexual dysfunction (n = 20). Group 1: Patients with IBS without sexual dysfunction (n = 20). The assignment of patients with IBS to the study group with and without sexual dysfunction will be according to the consecutive order in which they present to their clinic visit and after determining the Global Assessment of the Female Sexual Function Index.
Sample Size. The relationship between sample size, power and detectable difference was investigated, based on a previous study that evaluated the pain threshold recorded with the barostat in a problem group and a control group. The analysis was carried out comparing the two means with the unpaired Student's t, with two tails and an alpha value of 0.05. The anticipated standard deviation for each group resulted from the average between the standard deviation of the problem group (8.3) with the control group (8.8), resulting in a value of 8.5. The difference between means of the control group (35.9) and the problem group (27.2), resulted in 8.7. With this data a sample size of 16 subjects per group was obtained with a statistical power of 80%. Twenty women will be recruited to prevent the probable loss of 20%.
Measurements. Rome IV. The Rome IV, 2016criteria specify that abdominal pain must have occurred at least in the last 6 months with a frequency of at least once a week in the last 3 months and be related with at least 2 of the following characteristics: (a) Related to defecation, (b) Associated with changes in the frequency of defecation and / or (c) Associated with changes in the appearance of stool. The subtypes (constipation, diarrhea, mixed or indeterminate) are determined with the Bristol scale. Its application does not require special permissions.
Sexual function questionnaire. (Female Sexual Function Index, FSFI). The female sexual function index that we will use has been widely used in the Mexican population.40-42 It has 19 questions that evaluate 6 domains: Desire, arousal, lubrication, orgasm, satisfaction, and pain. The higher the score, the better the function. The optimal cut-off point to determine whether or not there is sexual dysfunction has been determined at 24.95 (sensitivity 64.15% and specificity of 75.76%). Does not require application permits.
General quality of life questionnaire (Short Form 36, SF-36). The SF-36 questionnaire has been adapted to the Mexican population and consists of 36 questions that assess 8 domains: physical function, physical role, body pain, general health, vitality, role emotional and mental health. The studies published on the characteristics of the Spanish version of the SF-36 provide enough evidence on its reliability, validity and sensitivity. Does not require application permits.
Specific Quality of Life Questionnaire for Irritable Bowel Syndrome (IBS-QOL) Developed in 199545 it has been used and widely validated in the Mexican population. It consists of 34 questions on a Likert scale from 1 to 5. It measures: Dysphoria, interference with activity , body image, health concern, food avoidance, social reaction, sexual concern and social relationship. The total score and scores in each dimension are converted on a scale from 0 to 100. Higher values indicate a better health-related quality of life. This questionnaire is copyrighted in favor of the MAPI institute.
Barostat Visceral sensitivity will be evaluated using a rectal barostat. After an overnight fast, a warm water enema will be performed 60 to 120 minutes before the study. Subjects will be studied without sedation and in the left lateral decubitus position. A rectal barostat distention will be placed 5 cm above the anal margin. Before starting the distension test, the subject will be warned that a rectal stimulus will be applied without her knowledge and when the light is illuminated on the perception panel, she must indicate her degree of pain perception. Gradual isobaric distention will be performed with increases of 4 mmHg from IOP. Strains will be performed to a grade 5 sensation or up to 50 mmHg (maximum strain pressure) or at the request of the subject. Each distension will be 1 minute in duration, and a 1 minute rest period will be observed between each step. At each pressure step, the volume of the bag will be recorded to assess rectal compliance. After 45 seconds of each distension step the light on the perception panel will illuminate to request the degree of rectal sensation of the subject under study. The intensity of the sensation will be quantified according to the control panel with numerical scales: 0 no sensation; 1 first sensation; 2 sensation of gas; 3 sensation of defecation; 4 mild pain; 5 moderate pain and 6: severe pain. Between each distension the pressure will return to the internal operating pressure. After this first phase, previously standardized foods will be taken. The meal will consist of 831 kcal and will be made with potato (100 g), mayonnaise (20 g), ham (100 g), margarine (20 g) and pineapple juice (250 ml). Each subject will consume the food completely in a maximum of 15 minutes. Thirty minutes after finishing the food, the postprandial tone and MLA will be measured.
STATISTIC ANALYSIS Parametric data will be compared using Student's t test. Nonparametric data will be compared using the Mann-Whitney U test. Symptoms and percentages will be evaluated with Fisher's exact test or chi square. The associations between data will be analyzed with the Spearman and Pearson correlation tests. The data will express the mean ± standard deviation and in percentages. Alpha = 0.05.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Irritable Bowel Syndrome with Sexual Dysfunction We use Rome IV criteria, scale bristol and the female sexual fuction to establish IBS and sexual dysfunction diagnosis, and SF-36 to determinated quality of life. |
Diagnostic Test: Blood analyses and coprological
We will take a blood and stool sample
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Irritable Bowel Syndrome without Sexual Dysfunction We use Rome IV criteria, scale bristol and the female sexual fuction to establish IBS and sexual dysfunction diagnosis, and SF-36 to determinated quality of life. |
Diagnostic Test: Blood analyses and coprological
We will take a blood and stool sample
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Outcome Measures
Primary Outcome Measures
- Change on barostat study during menstrual cycle [Second and third visit: Day 7 and day 21 of the menstrual cycle]
In this procedure, a small bag is placed in the rectum which is connected to a computer. This computer will insufflate air (in mL), measuring the pressure (in mmHg) inside the viscus (in this case the rectum) all time. With this system, a very precise feedback system is created allowing decrease or increase the pressure inside the rectum and thereby provoke the perception in the patient of different sensations. With the barostat we can simulate what happens when the stool reaches the rectum. Thus, the patient can report a first sensation, gas sensation, the need to defecate and even pain (mild, moderate or intense)
Secondary Outcome Measures
- General Quality of Life questionnaire (SF-36, Short Form-36) [Baseline]
This questionnaire consists of 36 questions that evaluate 8 domains (Items): physical function (10), physical role (4), body pain (2), general health (5), vitality (4), social function (2), role emotional (3) and mental health (5). Additionally, the SF-36 has a transition item that asks about the change in general health status compared to the previous year. Items are coded, aggregated and transformed on a scale from 0 (worst health status for that dimension) to 100 (best health status). Scores for the physical and emotional scale can also be calculated through an orthogonal approach
- Specific Quality of Life questionnaire (IBS-QOL, Irritable Bowel Syndrome-Quality of Life) [Baseline]
This questionnaire consists of 34 questions on a Likert scale from 1 to 5. It measures a total score and 8 dimensions (items): Dysphoria (8), interference with activity (7), body image (4), concern for health ( 3), food avoidance (3), social reaction (4), sexual concern (2) and social relationship (3). The total score and the scores in each dimension are converted on a scale from 0 to 100. Higher values indicate a better health-related quality of life
Eligibility Criteria
Criteria
Inclusion Criteria:
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-18 Years And Older,
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-Meet The Diagnostic Criteria Of Roma Iv For Ibs ,
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- Agreeing To Participate In The Study And Sign Informed Consent
Exclusion Criteria:
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-Patient With Non-Ibs-Related Visceral Neuropathy
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- Prokinetic And/Or Antidepressant Treatment Within 3 Months
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- Patients With Gastrointestinal Or Ibs-Related Disease
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- Patients With Severe Heart, Kidney And/Or Systemic Diseases
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- Pregnant Or Nursing Patients
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hospital General de Mexico
- Miguel Motola Kuba
- María de Fátima Higuera de la Tijera
- Hector Batalla Casimiro
- Yoshua Flores Bravo
Investigators
- Principal Investigator: Santiago Camacho, MD, MSc, 6761
Study Documents (Full-Text)
None provided.More Information
Publications
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