Fibromyalgia, Gastrointestinal Disease
Conditions
Keywords
probiotic, efficacy, tolerability
Brief summary
The study evaluated the efficacy and tolerability of probiotic VSL#3 for the treatment of gastrointestinal symptoms in patients with fibromyalgia; 50% of the participants received probiotic and the remaining 50% received matching placebo in a double-blind, randomized design.The treatment was administered during a 12-week period and the participants were followed for an additional 12-week period in order to follow the evolution after treatment.
Detailed description
Many patients with fibromyalgia experience associated gastrointestinal symptomatology such as abdominal pain, abdominal bloating, meteorism, diarrhea and/or constipation. To date there is not any specific treatment for these symptoms that markedly impair the quality of life of these subjects. This trial intended to investigate if the addition of a polymicrobial probiotic product, which has shown efficacy in patients with irritable bowel syndrome, was also be useful to ameliorate the gastrointestinal symptomatology of patients with fibromyalgia.
Interventions
DIETARY_SUPPLEMENTVSL#3
sachets containing probiotic
DIETARY_SUPPLEMENTPlacebo
sachets containing placebo
Sponsors
Actial Farmaceutica S.r.l.
Ferring Pharmaceuticals
Elena Pita Calandre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* diagnosed of fibromyalagia * experiencing at least 3 chronic gastrointestinal symptoms * signed informed consent to participate * accept to not change previously prescribed treatment during study duration
Exclusion criteria
* mental illness excepting depression * severe organic disease * additional gastrointestinal disease excepting irritable bowel syndrome * pregnancy * breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change, From Baseline to Endpoint (12 Weeks) in the Composite Score of Abdominal Pain, Abdominal Bloating and Metheorism Each One Measured in a 0-10 Visual Analog Scale | baseline and twelve weeks after treatment | Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 12 score - baseline score) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Insomnia Severity Inventory (ISI) | baseline and twelve weeks after treatment | The ISI is a self-reported, validated questionnaire that measures the severity of sleep disturbances in a scale ranging from 0 to 28 points: higher scores indicate more severe sleep disturbance |
| Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Patient Health Questionnaire (PHQ-9) | baseline and twelve weeks after treatment | PHQ-9 is a self-reported, validated questionnaire that measures the severity of depression in a scale ranging from 0 to 27 points; higher scores indicate more severe depression. Change = (week 12 score - baseline score) |
| Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 PCS | baseline and twelve weeks after treatment | The SF-36 is a self-reported, validated questionnaire evaluating the general health quality in a scale ranging from 0 to 100 points; it evaluates 8 heath domains that yield two summary measures: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Higher scores indicate better general health quality. Change = (week 12 score - baseline score). |
| Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 MCS | baseline and 12 weeks after treatment | The SF-36 is a self-reported, validated questionnaire evaluating the general health quality in a scale ranging from 0 to 100 points; it evaluates 8 heath domains that yield two summary measures: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Higher scores indicate better general health quality. Change = (week 12 score - baseline score). |
| Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Fibromyalgia Impact Questionnaire Revised (FIQR) | baseline and twelve weeks after treatment | The FIQR is a self-reported, validated questionnaire that evaluates the severity of fibromyalgia symptomatology in a scale ranging from 0 to 100 points; the higher the score, the worse the severity of the disease. Change = (week 12 score - baseline score) |
| Change From Week 12 to Week 16 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | Week 12 to week 16 | Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 16 score - week 12 score) |
| Change From Week 12 to Week 20 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | Week 12 to week 20 | Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 20 score - week 12 score) |
| Change From Week 12 to Week 24 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | Week 12 to week 24 | Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 24 score - week 12 score) |
| Number of Patients Considered as Responders to Treatment | Baseline and 12 weeks after treatment | Patients that showed at least a a 30% reduction in the score of the primary variable, i.e. the composite ccore of abdominal pain, abdominal bloating and metheorism each one measured in a 0-10 Visual Analog Scale, were considered as responders to treatment. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VSL#3 probiotic VSL#3, 2 sachets b.i.d for 3 months
VSL#3: sachets containing probiotic | 54 |
| Placebo matched placebo, 2 sachets b.i.d for 3 months
Placebo: sachets containing placebo | 56 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 6 |
| Overall Study | Lack of Efficacy | 3 | 4 |
| Overall Study | Lost to Follow-up | 7 | 7 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Surgery or quarantined due to Covid-19 | 5 | 7 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | VSL#3 |
|---|---|---|---|
| Age, Continuous | 55.5 years STANDARD_DEVIATION 8.6 | 55.6 years STANDARD_DEVIATION 8.1 | 56 years STANDARD_DEVIATION 7.5 |
| Fibromyalgia diagnosis - Fibromyalgia Score | 26.2 scores on a scale STANDARD_DEVIATION 3.5 | 25.7 scores on a scale STANDARD_DEVIATION 3.9 | 25.3 scores on a scale STANDARD_DEVIATION 4.3 |
| Fibromyalgia diagnosis - Symptom Severity Score | 9.7 scores on a scale STANDARD_DEVIATION 1.7 | 9.5 scores on a scale STANDARD_DEVIATION 1.9 | 9.3 scores on a scale STANDARD_DEVIATION 2 |
| Fibromyalgia diagnosis - Widespread Pain Index (WPI) total score | 16.5 scores on a scale STANDARD_DEVIATION 2.6 | 16.2 scores on a scale STANDARD_DEVIATION 2.8 | 15.9 scores on a scale STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 56 Participants | 110 Participants | 54 Participants |
| Sex: Female, Male Female | 55 Participants | 107 Participants | 52 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
| Weight (Kg) | 71.2 kgs STANDARD_DEVIATION 13.4 | 72.2 kgs STANDARD_DEVIATION 15.6 | 73.3 kgs STANDARD_DEVIATION 17.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 56 |
| other Total, other adverse events | 20 / 54 | 19 / 56 |
| serious Total, serious adverse events | 0 / 54 | 0 / 56 |
Outcome results
Primary
Change, From Baseline to Endpoint (12 Weeks) in the Composite Score of Abdominal Pain, Abdominal Bloating and Metheorism Each One Measured in a 0-10 Visual Analog Scale
Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 12 score - baseline score)
Time frame: baseline and twelve weeks after treatment
Population: Intent to Treat Population (all patients with at least a post-baseline evaluation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change, From Baseline to Endpoint (12 Weeks) in the Composite Score of Abdominal Pain, Abdominal Bloating and Metheorism Each One Measured in a 0-10 Visual Analog Scale | -6.5 score on a scale | Standard Deviation 9.5 |
| Placebo | Change, From Baseline to Endpoint (12 Weeks) in the Composite Score of Abdominal Pain, Abdominal Bloating and Metheorism Each One Measured in a 0-10 Visual Analog Scale | -5.4 score on a scale | Standard Deviation 6.6 |
Secondary
Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 MCS
The SF-36 is a self-reported, validated questionnaire evaluating the general health quality in a scale ranging from 0 to 100 points; it evaluates 8 heath domains that yield two summary measures: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Higher scores indicate better general health quality. Change = (week 12 score - baseline score).
Time frame: baseline and 12 weeks after treatment
Population: Intent to Treat Population (all patients with at least a post-baseline evaluation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 MCS | 0.8 score on a scale | Standard Deviation 12.4 |
| Placebo | Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 MCS | 1.9 score on a scale | Standard Deviation 12.2 |
Secondary
Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 PCS
The SF-36 is a self-reported, validated questionnaire evaluating the general health quality in a scale ranging from 0 to 100 points; it evaluates 8 heath domains that yield two summary measures: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Higher scores indicate better general health quality. Change = (week 12 score - baseline score).
Time frame: baseline and twelve weeks after treatment
Population: Intent to Treat Population (all patients with at least a post-baseline evaluation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 PCS | 4.5 score on a scale | Standard Deviation 8 |
| Placebo | Change, From Baseline to Endpoint (12 Weeks) in the Short-Form Health Survey SF-36 PCS | 2.2 score on a scale | Standard Deviation 6.3 |
Secondary
Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Fibromyalgia Impact Questionnaire Revised (FIQR)
The FIQR is a self-reported, validated questionnaire that evaluates the severity of fibromyalgia symptomatology in a scale ranging from 0 to 100 points; the higher the score, the worse the severity of the disease. Change = (week 12 score - baseline score)
Time frame: baseline and twelve weeks after treatment
Population: Intent to Treat Population (all patients with at least a post-baseline evaluation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Fibromyalgia Impact Questionnaire Revised (FIQR) | -7.2 score on a scale | Standard Deviation 12.5 |
| Placebo | Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Fibromyalgia Impact Questionnaire Revised (FIQR) | -12.5 score on a scale | Standard Deviation 14.1 |
Secondary
Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Insomnia Severity Inventory (ISI)
The ISI is a self-reported, validated questionnaire that measures the severity of sleep disturbances in a scale ranging from 0 to 28 points: higher scores indicate more severe sleep disturbance
Time frame: baseline and twelve weeks after treatment
Population: Intent to Treat Population (all patients with at least a post-baseline evaluation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Insomnia Severity Inventory (ISI) | -1.7 score on a scale | Standard Deviation 5.9 |
| Placebo | Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Insomnia Severity Inventory (ISI) | -1.2 score on a scale | Standard Deviation 4 |
Secondary
Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Patient Health Questionnaire (PHQ-9)
PHQ-9 is a self-reported, validated questionnaire that measures the severity of depression in a scale ranging from 0 to 27 points; higher scores indicate more severe depression. Change = (week 12 score - baseline score)
Time frame: baseline and twelve weeks after treatment
Population: Intent to Treat Population (all patients with at least a post-baseline evaluation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Patient Health Questionnaire (PHQ-9) | -2.2 score on a scale | Standard Deviation 7.2 |
| Placebo | Change, From Baseline to Endpoint (12 Weeks) in the Total Score of the Patient Health Questionnaire (PHQ-9) | -2.5 score on a scale | Standard Deviation 4.2 |
Secondary
Change From Week 12 to Week 16 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment
Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 16 score - week 12 score)
Time frame: Week 12 to week 16
Population: Patients considered as responders to treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change From Week 12 to Week 16 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | 2.0 units on a scale | Standard Deviation 5.2 |
| Placebo | Change From Week 12 to Week 16 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | 1.7 units on a scale | Standard Deviation 4.2 |
Secondary
Change From Week 12 to Week 20 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment
Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 20 score - week 12 score)
Time frame: Week 12 to week 20
Population: Patients considered as responders to treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change From Week 12 to Week 20 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | 1.0 units on a scale | Standard Deviation 3.7 |
| Placebo | Change From Week 12 to Week 20 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | 3.4 units on a scale | Standard Deviation 5.4 |
Secondary
Change From Week 12 to Week 24 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment
Visual analogue scales are frequently used to evaluate subjective symptoms; they range from 0 (no symptom at all) to 10 (worst possible intensity of the symptom) points. In the present case the three most frequent abdominal symptoms reported by patients with fibromyalgia have been selected to compose the primary outcome variable. Total symptoms range was 0 to 30 points. Change = (week 24 score - week 12 score)
Time frame: Week 12 to week 24
Population: Patients considered as responders to treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VSL#3 | Change From Week 12 to Week 24 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | 1.3 units on a scale | Standard Deviation 3.6 |
| Placebo | Change From Week 12 to Week 24 (Follow-up Period) in the Composite Score of Abdominal Pain, Bloating and Metheorism Among Responders After Discontinuing the Study Treatment | 4.1 units on a scale | Standard Deviation 5.5 |
Secondary
Number of Patients Considered as Responders to Treatment
Patients that showed at least a a 30% reduction in the score of the primary variable, i.e. the composite ccore of abdominal pain, abdominal bloating and metheorism each one measured in a 0-10 Visual Analog Scale, were considered as responders to treatment.
Time frame: Baseline and 12 weeks after treatment
Population: Intent to Treat Population (all patients with at least a post-baseline evaluation)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VSL#3 | Number of Patients Considered as Responders to Treatment | 27 participants |
| Placebo | Number of Patients Considered as Responders to Treatment | 22 participants |