SNPMiner Trials by Shray Alag


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Report for Mutation S977F

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials


1 Nutritional Impact of Ivacaftor Treatment in 6 Month to 2 Year Old Children With CF Gating Mutations

The purpose of this research study is to determine the effects of clinically prescribed ivacaftor treatment on 6-24 month old children with CF and gating mutations on sleeping energy expenditure, growth status and gut health and function.

NCT03783286 Cystic Fibrosis Drug: Ivacaftor
MeSH: Cystic Fibrosis

Each value will be used to calculate the growth velocity percentile of the subjects over the course of 12 weeks on ivacaftor treatment compared to baseline.. Inclusion Criteria: - Cystic fibrosis with at least one CFTR gating mutation (E56K, G178R, S549R, S977F, F1074L, 2789+5G→A,P67L, E193K, G551D, F1052V, D1152H, 3272-26A→G, R74W, L206W, G551S, K1060T, G1244E, 3849+10kbC→T, D110E, R347H, D579G, A1067T, S1251N, D110H, R352Q, 711+3A→G, G1069R, S1255P, R117C, A455E, E831X, R1070Q, D1270N, R117H, S549N, S945L, R1070W, G1349D) approved for treatment - Age: 6-24 months of age - In their usual state of good health - A clinical decision has been made for subject to begin ivacaftor treatment - Family committed to the 4 to 6 month study protocol with visits to CHOP that will last 2 or 3 days for the baseline visit (Visit 1) prior to ivacaftor and the 12 week visit (Visit 3) after clinically prescribed ivacaftor treatment has begun, and will last 2 days for the 6 week visit (Visit 2) after ivacaftor treatment has begun. --- E56K --- --- G178R --- --- S549R --- --- S977F ---

Exclusion Criteria: - On parenteral nutrition - Use of any medications which are as inhibitors or inducers of cytochrome P450 (CYP) 3A - Liver function tests elevated above 3x the reference range for age and sex - Other illness affecting growth or nutritional status - Other contraindications described for ivacaftor therapy Inclusion Criteria: - Cystic fibrosis with at least one CFTR gating mutation (E56K, G178R, S549R, S977F, F1074L, 2789+5G→A,P67L, E193K, G551D, F1052V, D1152H, 3272-26A→G, R74W, L206W, G551S, K1060T, G1244E, 3849+10kbC→T, D110E, R347H, D579G, A1067T, S1251N, D110H, R352Q, 711+3A→G, G1069R, S1255P, R117C, A455E, E831X, R1070Q, D1270N, R117H, S549N, S945L, R1070W, G1349D) approved for treatment - Age: 6-24 months of age - In their usual state of good health - A clinical decision has been made for subject to begin ivacaftor treatment - Family committed to the 4 to 6 month study protocol with visits to CHOP that will last 2 or 3 days for the baseline visit (Visit 1) prior to ivacaftor and the 12 week visit (Visit 3) after clinically prescribed ivacaftor treatment has begun, and will last 2 days for the 6 week visit (Visit 2) after ivacaftor treatment has begun. --- E56K --- --- G178R --- --- S549R --- --- S977F ---

Primary Outcomes

Description: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's SEE. Using indirect calorimetry, SEE will be assessed using a computerized metabolic cart Vmax ENCORE at each protocol visit while the child is asleep. SEE will be assessed in the morning if possible and careful note of previous feeding of the child, including the time of day, amount of food, and feeding interval prior to test

Measure: Sleeping Energy Expenditure

Time: 12 Weeks

Description: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's BMI. Investigators will compare the results to BMI Z scores over 12 weeks compared to baseline.

Measure: Anthropometric Assessment

Time: 12 Weeks

Secondary Outcomes

Description: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's pancreatic function. Pancreatic function will be assessed at two visits by obtaining spot stool samples with fecal elastase 1. The concentration of fecal elastase I is indicative of pancreatic function.

Measure: Fecal Elastase I/Pancreatic Function

Time: 12 Weeks

Description: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's gut health and function. Spot stool samples will be obtained to determine fecal calprotectin, a marker for gut inflammation.

Measure: Fecal Calprotectin/Gut Inflammation

Time: 12 Weeks

Description: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's dietary fat absorption. A total plasma fatty acid panel will be assessed to measure the change in status of 22 fatty acids, the concentration of plasma fatty acids is indicative of dietary fat absorption.

Measure: Plasma Total Fatty Acids:

Time: 4 to 6 months

Other Outcomes

Description: Three day weighed food record will be obtained and to determine changes in dietary caloric intake and micro and macronutrient intake over the course of 12 weeks on ivacaftor treatment. The weighed food in grams will be used to determine the calories consumed, as well as calories from fat. The caloric intake will be used to determine micro and macro nutrient intake.

Measure: Dietary Intake

Time: 12 Weeks

Description: Investigators will examine the changes in serum vitamin A, E, D and K concentrations after 12 weeks of Ivacaftor treatment. Additionally, investigators will examine the changes in total serum bile acids concentration and 14 bile acid species. Additionally, serum calprotectin will be obtained as a marker of lung and gut inflammation.

Measure: Serum fat soluble vitamins A, D, E and K, bile acids, and serum calprotectin

Time: 12 Weeks

Description: Investigators will measure body composition to determine muscle and fat store changes over the course of 12 weeks on ivacaftor treatment compared to baseline.

Measure: Muscle/Fat Stores

Time: 12 Weeks

Description: Investigators will observe the changes in growth status/growth velocity. This will be assessed amongst three different measurements- length (cm), weight (kg) and head circumference (cm). Each value will be used to calculate the growth velocity percentile of the subjects over the course of 12 weeks on ivacaftor treatment compared to baseline.

Measure: Growth Status/Growth Velocity

Time: 12 Weeks

2 Response to CFTR-modulators in Intestinal Organoids of Patients With CF Having at Least One R334W Mutation

In contrary to what is seen in FRT cells, rectal organoids of patients with a R334W mutation do respond to CFTR modulators ivacaftor and lumacaftor. The present study will investigate the response to modulators in organoids of 30 patients with CF and a R334W mutation, to allow further stratificaton for a future clinical trial assessing the clinical effect of ivacaftor/tezacaftor in patients with CF and a R334W mutation.

NCT04254705 Cystic Fibrosis Procedure: Rectal Biopsy
MeSH: Cystic Fibrosis

Exclusion Criteria: - A potential subject who meets any of the following criteria will be excluded from participation: 1. Subject has one of the following CFTR-mutations: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, R117H, P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A>G, S945L, S977F, R1070W, D1152H, 2789+5G>A, 3272 26A>G, 3849+10kbC>T 2. A history of hemorrhoids and recent rectal bleeding 3. FEV1 above 90% predicted or below 30% predicted during stable disease 4. History of lung transplantation. --- G551D --- --- G1244E --- --- G1349D --- --- G178R --- --- G551S --- --- S1251N --- --- S1255P --- --- S549N --- --- S549R --- --- R117H --- --- P67L --- --- R117C --- --- L206W --- --- R352Q --- --- A455E --- --- D579G --- --- S945L --- --- S977F ---

Primary Outcomes

Description: Response to tezacaftor+ivacaftor in the Forskolin Induced Swelling (FIS) assay in rectal organoids

Measure: Response to CFTR-modulator in Intestinal Organoids: Increase in Forskolin induced swelling by addition of tezacaftor+ivacaftor after stimulation with Forskolin (0.8 µmol/L)

Time: At study completion (when rectal biopsy is performed or when organoids are retrieved from the biobank and FIS has been performed), an average of 2 months


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