Probiotics and Corticosteroids for Treating Periodic Fever, Aphthous Stomatitis, Pharyngitis, Cervical Adenitis (PFAPA)

NCT02535962 | Withdrawn Phase 2

• 1 other identifier: 15-017
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of study is to see if adding probiotics to corticosteroid treatment for children with PFAPA could improve the health and daily of patients through reduction in febrile period frequency and length, along with concomitant reduction of associated symptoms. Current standard of care incorporates the administration of corticosteroids; however, while limiting the symptoms associated with PFAPA, corticosteroid use has been shown to increase the frequency at which these symptoms occur. Investigators hypothesize that administration of probiotics along with corticosteroids will work to decrease the frequency at which the febrile episodes occur. Additionally, probiotics may decrease the maximal fever experienced during these episodes, amount of corticosteroid needed to control the symptoms, average length of the episodes, and the number of patients who ultimately undergo tonsillectomy due to unsuccessful treatment with medication.

Conditions

Periodic Fever; Aphthous Stomatitis; Pharyngitis; Cervical Adenitis

Keywords

PFAPA

Outcome Measures

Primary Outcomes (2)

• Effects of the investigational treatment

  Increased healthy intervals between cyclic febrile episodes in patients with PFAPA compared to patients being solely treated with corticosteroids.

  Time to event: number of fever-free days will be calculated, as well as the average number of days between fever cycles from baseline to end of study which is 12 months.

• Safety of the investigational treatment - reported descriptively as percentages of patients experiencing adverse and serious adverse events.

  Safety will be reported descriptively as percentages of patients experiencing adverse and serious adverse events.

  Time to event: number of fever-free days will be calculated, as well as the average number of days between fever cycles from baseline to end of study which is 12 months.

Secondary Outcomes (4)

• Maximal fever experienced during a PFAPA febrile episode will be recorded as an average of the peak temperature recorded during each episode throughout the year and compared between the study groups

  Maximal fever experienced during a PFAPA febrile episode will be recorded as an average of the peak temperature recorded during each episode throughout the year

• Number of administrations of corticosteroid necessary for treatment of PFAPA syndrome, recorded as the average number of administrations per fever episode throughout the year

  Number of administrations of corticosteroid necessary for treatment of PFAPA syndrome, recorded as the average number of administrations per fever episode throughout the year

• The average duration of the individual cyclic febrile episodes

  average duration of the individual cyclic febrile episodes in patients with PFAPA will be assessed from baseline to the end of study which is 1 year

• The number of patients undergoing tonsillectomy will be compared between the study groups

  At any time during the study from baseline to end of study, which is 12 months this will recorded

Study Arms (2)

Corticosteriod + Probiotic Treatment

EXPERIMENTAL

Corticosteroid dosing of 1 mg/kg of body weight given once at the onset of the febrile period, repeated once within 24 hours if necessary, but no more than two doses per cycle. The second dose of corticosteroid treatment is only to be given within one day following the initial dosage if the fever persists. Investigational drug (Intervention is Lactobacillus acidophilus and Bifidobacterium lactis): Patients will be instructed to take one sachet of the study product mixed into a 60 ml of water that is not hot. Each sachet will contain Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 at a dose of 5\*109 CFU of each strain. The investigational product will be taken daily for the duration of the study, which is a year.

Biological: Lactobacillus acidophilus and Bifidobacterium lactis

Corticosteriod + PlaceboTreatment

PLACEBO COMPARATOR

Corticosteroid dosing of 1 mg/kg of body weight given once at the onset of the febrile period, repeated once within 24 hours if necessary, but no more than two doses per cycle. The second dose of corticosteroid treatment is only to be given within one day following the initial dosage if the fever persists. Placebo: will be taken daily and patients will be instructed to take one sachet of placebo mix into 60ml of water that is not to hot. The placebo will be taken daily for the duration of the study, which is one year. Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product.

Other: Placebo

Interventions

Lactobacillus acidophilus and Bifidobacterium lactis BIOLOGICAL

study product will be freeze dried and put into foil sachets

Also known as: HOWARU® Protect Kids

Corticosteriod + Probiotic Treatment

Placebo OTHER

Placebo will look and taste like the investigational product. This also will be provided in a foil sachets

Corticosteriod + PlaceboTreatment

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• diagnosis or confirmation of diagnosis of PFAPA from Dr. Bennett based on clinical or laboratory data
• is or will be undergoing treatment for PFAPA at CCMC
• agrees to the consent and, if necessary, assent forms
• is between 1 and 12 years of age

You may not qualify if:

• is currently taking another probiotic regularly (\>=2 times/ week)
• is allergic to ingredients in the probiotic or placebo
• may react adversely to the probiotic due to any form of immune deficiency or chronic disease including pulmonary, renal, cardiac disorders including underlying structural heart disease, gastrointestinal disease, or diabetes
• is not a proficient English speaker
• does not agree to the consent and/or assent forms
• patients who use antibiotics or have used them within a month of the study start

Sponsors & Collaborators

• Connecticut Children's Medical Center: lead
• DuPont Nutrition and Health: collaborator

MeSH Terms

Conditions

Hereditary Autoinflammatory Diseases; Stomatitis, Aphthous; Pharyngitis

Interventions

Lacteol

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Stomatitis; Mouth Diseases; Stomatognathic Diseases; Respiratory Tract Infections; Infections; Pharyngeal Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Study Officials

• Nicholas Bennett, MBBChir PhD

  Connecticut Children's Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director of Infectious Disease Department

Study Record Dates

• First Submitted: August 20, 2015
• First Posted: August 31, 2015
• Study Start: October 1, 2016
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: January 24, 2018

Record last verified: 2018-01