Cystic FibrosisPhase 3NCT01956916
Probiotics in Cystic Fibrosis
A Phase 3 study testing Lactobacillus rhamnosus GG in people with Cystic Fibrosis, run by Federico II University at 5 sites in Italy.
Trial summary
Cystic fibrosis (CF) is a complex systemic disease that mainly involves the respiratory and gastrointestinal (GI) tracts. The polymicrobial community composition of respiratory and GI tracts is influenced by both genetic and environmental factors. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Lactobacillus rhamnosus GG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 5 sitesItaly
- Study dates
- Oct 2010to Dec 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- A confirmed diagnosis of CF documented by sweat chloride test over 60 mmol/L and confirmed by genotype analysis with the presence of F508del/F508del or F508del/other
- Boys and girls between 2 and 16 years of age
- Clinical stability at enrolment, defined as no clinical evidence of acute exacerbation, no modifications in the therapeutic regimen and no hospitalization in the last 2 weeks
- Pancreatic insufficiency
- Basal Forced Expiratory Volume 1 second above 50% of predicted value
Who cannot join
- Colonization of respiratory tract with Burkholderia cepacia spp.
- Steroid therapy within one month before enrolment
- Pregnancy and fertile women taking oral contraceptives
- Parenteral or oral antibiotics therapy within 2 weeks before enrolment
- Regular assumption of probiotics
- Regular assumption of azythromycin
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Italy5 sites
- Department of Paediatric Medicine, CF Center, "A. Meyer" Children's Hospital
Florence
Dipartimento di Pediatria - Università Di Messina
Messina
Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
Milan
Università degli studi di Napoli "Federico II"
Naples
Ospedale "Bambino Gesù" - Roma
Rome
About this study
Official title: Effects of LGG Administration in Children With Cystic Fibrosis: A Randomized Controlled Trial
Cystic fibrosis (CF) is a complex systemic disease that mainly involves the respiratory and gastrointestinal (GI) tracts. The polymicrobial community composition of respiratory and GI tracts is influenced by both genetic and environmental factors. Children with CF may harbor an abnormal intestinal microflora, because of altered cystic fibrosis transmembrane conductance regulator (CFTR) function and heavy drug load (antibiotics, pancreatic enzymes and acid suppressors). The investigators have previously demonstrated that intestinal inflammation is highly frequent in CF children, being a major feature of intestinal involvement. In addition, specific probiotics significantly improved airway and GI inflammation in a preliminary trial. The investigators aim to characterize intestinal and respiratory microflora in CF patients and to investigate the effects of daily Lactobacillus GG (LGG) supplementation on both GI and airway microflora and the eventual relationship between probiotic assumption and clinical and inflammation markers. The investigators aim is to eventually improve the quality of life of CF patients, who often suffer from intestinal and respiratory progressive disease, through a non invasive intervention consisting in the supplementation of probiotic bacteria.
- Conditions
- Cystic Fibrosis
- Being tested
- Lactobacillus rhamnosus GG, placebo
- Keywords
- Pulmonary exacerbation, Inflammation, Intestinal microbiota
- Medical subject headings
- Cystic Fibrosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus rhamnosus GGDietary supplement
Also called LGG
Capsules containing lyophilized 6x10^9 Colony Forming Units (CFU)/die LGG, (60mg) maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg)
1 cps/die for 12 months
placeboDietary supplement
Capsules containing maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg)
1 cps/die for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Probiotics | Experimental | Capsules containing lyophilized 6x10^9 Colony Forming Units (CFU)/die of Lactobacillus rhamnosus GG (LGG) Receives: Dietary Supplement: Lactobacillus rhamnosus GG |
| Placebo | Placebo comparator | Capsules containing maltodextrin Receives: Dietary Supplement: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the incidence of pulmonary exacerbations from baseline to 12 months of treatment
The incidence of pulmonary exacerbation is assessed every six months. First evaluation from baseline to 6 months of observation. Second evaluation from randomization ( placebo/LGG) to 6 months of treatment and third evaluation after 12 months of treatment
Measured: every six months up to 18 months
Change of intestinal inflammation from baseline to 12 months of treatment
Assessment of intestinal inflammation is performed four times. First time at enrollment, second time at the end of six months of observation. Third time after six months of treatment and fourth time after 12 months of treatment.
Measured: every six months up to 18 months
Secondary outcomes (2)
Change in the incidence of hospital admission from baseline to 12 months of treatment
The incidence of hospital admission is assessed every six months. First evaluation from baseline to 6 months of observation. Second evaluation from randomization ( placebo/LGG) to 6 months of treatment and third evaluation after 12 months of treatment
Measured: every six month up to 18 months
change in pulmonary function from baseline to 12 months of treatment (measured by Forced Expiratory Volume 1 sec (FEV1))
Assessment of pulmonary function is performed four times. First time at enrollment, second time at the end of six months of observation. Third time after six months of treatment and fourth time after 12 months of treatment.
Measured: every six months up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2013 (estimated)
- Study startOct 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alfredo Guarino, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01956916
- Sponsor's protocol ID
- CF001
- Other IDs
- 2009-011289-27, 2009
- Status last verified
- Sep 2015
- First submitted
- 23 Sep 2013
- Last updated
- 23 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bruzzese E, Raia V, Spagnuolo MI, Volpicelli M, De Marco G, Maiuri L, Guarino A. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin Nutr. 2007 Jun;26(3):322-8. doi: 10.1016/j.clnu.2007.01.004. Epub 2007 Mar 13.
PubMed 17360077Bruzzese E, Raia V, Gaudiello G, Polito G, Buccigrossi V, Formicola V, Guarino A. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther. 2004 Oct 1;20(7):813-9. doi: 10.1111/j.1365-2036.2004.02174.x.
PubMed 15379842Raia V, Maiuri L, de Ritis G, de Vizia B, Vacca L, Conte R, Auricchio S, Londei M. Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients. Pediatr Res. 2000 Mar;47(3):344-50. doi: 10.1203/00006450-200003000-00010.
PubMed 10709733Lucidi V, Alghisi F, Raia V, Russo B, Valmarana L, Valmarana R, Coruzzo A, Beschi S, Dester S, Rinaldi D, Maglieri M, Guidotti ML, Ravaioli E, Pesola M, De Alessandri A, Padoan R, Grynzich L, Ratclif L, Repetto T, Ambroni M, Provenzano E, Tozzi AE, Colombo C. Growth assessment of paediatric patients with CF comparing different auxologic indicators: A multicentre Italian study. J Pediatr Gastroenterol Nutr. 2009 Sep;49(3):335-42. doi: 10.1097/MPG.0b013e31818f0a39.
PubMed 19543116Miragoli F, Federici S, Ferrari S, Minuti A, Rebecchi A, Bruzzese E, Buccigrossi V, Guarino A, Callegari ML. Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota. FEMS Microbiol Ecol. 2017 Feb;93(2):fiw230. doi: 10.1093/femsec/fiw230. Epub 2016 Nov 2.
PubMed 27810876
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of LGG Administration in Children With Cystic Fibrosis: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01956916
- Acronym / sponsor ID
- CF001
- Conditions
- Cystic Fibrosis
- Keywords
- Pulmonary exacerbation, Inflammation, Intestinal microbiota
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 8 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cystic fibrosis (CF) is a complex systemic disease that mainly involves the respiratory and gastrointestinal (GI) tracts. The polymicrobial community composition of respiratory and GI tracts is influenced by both genetic and environmental factors. Children with CF may harbor an abnormal intestinal microflora, because of altered cystic fibrosis transmembrane conductance regulator (CFTR) function and heavy drug load (antibiotics, pancreatic enzymes and acid suppressors). The investigators have previously demonstrated that intestinal inflammation is highly frequent in CF children, being a major feature of intestinal involvement. In addition, specific probiotics significantly improved airway and GI inflammation in a preliminary trial. The investigators aim to characterize intestinal and respiratory microflora in CF patients and to investigate the effects of daily Lactobacillus GG (LGG) supplementation on both GI and airway microflora and the eventual relationship between probiotic assumption and clinical and inflammation markers. The investigators aim is to eventually improve the quality of life of CF patients, who often suffer from intestinal and respiratory progressive disease, through a non invasive intervention consisting in the supplementation of probiotic bacteria.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotics | Experimental | Dietary Supplement: Lactobacillus rhamnosus GGCapsules containing lyophilized 6x10^9 Colony Forming Units (CFU)/die of Lactobacillus rhamnosus GG (LGG) |
| Placebo | Placebo comparator | Dietary Supplement: placeboCapsules containing maltodextrin |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- A confirmed diagnosis of CF documented by sweat chloride test over 60 mmol/L and confirmed by genotype analysis with the presence of F508del/F508del or F508del/other
- Boys and girls between 2 and 16 years of age
- Clinical stability at enrolment, defined as no clinical evidence of acute exacerbation, no modifications in the therapeutic regimen and no hospitalization in the last 2 weeks
- Pancreatic insufficiency
- Basal Forced Expiratory Volume 1 second above 50% of predicted value
Key exclusion criteria (6 listed)
- Colonization of respiratory tract with Burkholderia cepacia spp.
- Steroid therapy within one month before enrolment
- Pregnancy and fertile women taking oral contraceptives
- Parenteral or oral antibiotics therapy within 2 weeks before enrolment
- Regular assumption of probiotics
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactobacillus rhamnosus GGAlso: LGGCapsules containing lyophilized 6x10^9 Colony Forming Units (CFU)/die LGG, (60mg) maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg) 1 cps/die for 12 months | Dietary supplement | Probiotics |
| placeboCapsules containing maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg) 1 cps/die for 12 months | Dietary supplement | Placebo |
Primary outcome
Change in the incidence of pulmonary exacerbations from baseline to 12 months of treatment
Time frame: every six months up to 18 months
The incidence of pulmonary exacerbation is assessed every six months. First evaluation from baseline to 6 months of observation. Second evaluation from randomization ( placebo/LGG) to 6 months of treatment and third evaluation after 12 months of treatment
Change of intestinal inflammation from baseline to 12 months of treatment
Time frame: every six months up to 18 months
Assessment of intestinal inflammation is performed four times. First time at enrollment, second time at the end of six months of observation. Third time after six months of treatment and fourth time after 12 months of treatment.
2 secondary outcomes
Change in the incidence of hospital admission from baseline to 12 months of treatment
Time frame: every six month up to 18 months
change in pulmonary function from baseline to 12 months of treatment (measured by Forced Expiratory Volume 1 sec (FEV1))
Time frame: every six months up to 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2015.
- Background: PubMed 17360077Bruzzese E, Raia V, Spagnuolo MI, Volpicelli M, De Marco G, Maiuri L, Guarino A. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin Nutr. 2007 Jun;26(3):322-8. doi: 10.1016/j.clnu.2007.01.004. Epub 2007 Mar 13.
- Background: PubMed 15379842Bruzzese E, Raia V, Gaudiello G, Polito G, Buccigrossi V, Formicola V, Guarino A. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther. 2004 Oct 1;20(7):813-9. doi: 10.1111/j.1365-2036.2004.02174.x.
- Background: PubMed 10709733Raia V, Maiuri L, de Ritis G, de Vizia B, Vacca L, Conte R, Auricchio S, Londei M. Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients. Pediatr Res. 2000 Mar;47(3):344-50. doi: 10.1203/00006450-200003000-00010.
- Background: PubMed 19543116Lucidi V, Alghisi F, Raia V, Russo B, Valmarana L, Valmarana R, Coruzzo A, Beschi S, Dester S, Rinaldi D, Maglieri M, Guidotti ML, Ravaioli E, Pesola M, De Alessandri A, Padoan R, Grynzich L, Ratclif L, Repetto T, Ambroni M, Provenzano E, Tozzi AE, Colombo C. Growth assessment of paediatric patients with CF comparing different auxologic indicators: A multicentre Italian study. J Pediatr Gastroenterol Nutr. 2009 Sep;49(3):335-42. doi: 10.1097/MPG.0b013e31818f0a39.
- Derived from this study: PubMed 27810876Miragoli F, Federici S, Ferrari S, Minuti A, Rebecchi A, Bruzzese E, Buccigrossi V, Guarino A, Callegari ML. Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota. FEMS Microbiol Ecol. 2017 Feb;93(2):fiw230. doi: 10.1093/femsec/fiw230. Epub 2016 Nov 2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lactobacillus rhamnosus GG in people with Cystic Fibrosis, run by Federico II University at 5 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the incidence of pulmonary exacerbations from baseline to 12 months of treatment (time frame: every six months up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01956916, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2015.