Ignite Creation Date:
2024-05-06 @ 7:39 PM
Last Modification Date:
2024-10-26 @ 3:11 PM
Study NCT ID:
NCT06089265
Status:
COMPLETED
Last Update Posted:
2024-01-24
First Post:
2023-05-15
Brief Title:
Ketohexokinase Inhibition in Hereditary Fructose Intolerance
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
Short-term Safety and Efficacy of Ketohexokinase Inhibition in Patients With Hereditary Fructose Intolerance
Status:
COMPLETED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
KHKi in HFI
Brief Summary:
Hereditary fructose intolerance HFI is a rare inborn error of metabolism Patients with HFI develop acute abdominal pain nausea vomiting hypoglycemia and proximal tubular dysfunction upon consumption of a fructose containing food product In rare cases prolonged fructose consumption can even lead to liver and kidney failure Patients with HFI are therefore treated with a lifelong fructose-restricted diet Animal studies have shown that the clinical manifestations of HFI are abrogated upon inhibition of ketohexokinase KHK the enzyme that catalyses the first step in fructose metabolism
Recently PF-06835919 a KHK inhibitor KHKi was developed as a new treatment for non-alcoholic fatty liver disease The compound was well tolerated in several phase II clinical trials
It is hypothesized that PF-06835919 is also effective in patients with HFI
Recently PF-06835919 a KHK inhibitor KHKi was developed as a new treatment for non-alcoholic fatty liver disease The compound was well tolerated in several phase II clinical trials
It is hypothesized that PF-06835919 is also effective in patients with HFI
Detailed Description:
Rationale Hereditary fructose intolerance HFI is a rare inborn error of metabolism Patients with HFI develop acute abdominal pain nausea vomiting hypoglycemia and proximal tubular dysfunction upon consumption of a fructose containing food product In rare cases prolonged fructose consumption can even lead to liver and kidney failure Patients with HFI are therefore treated with a lifelong fructose-restricted diet Animal studies have shown that the clinical manifestations of HFI are abrogated upon inhibition of ketohexokinase KHK the enzyme that catalyses the first step in fructose metabolism
Recently PF-06835919 a KHK inhibitor KHKi was developed as a new treatment for non-alcoholic fatty liver disease The compound was well tolerated in several phase II clinical trials
It is hypothesized that PF-06835919 is also effective in patients with HFI Objective To study the effects of PF-06835919 on fructose tolerance and intrahepatic lipid content in patients with HFI Study design open-label pilot study Study population three adult patients with HFI will be treated with PF-06835919 Five adult healthy individuals will be included but not be treated as a reference Intervention if applicable Patients receive once daily in the morning three tablets of 100 mg PF-06835919 for 9 days They will subsequently be gradually exposed to increasing doses of either oral fructose or glucose in a blinded fashion Healthy individuals will only undergo oral fructose exposure as a reference Main study parametersendpoints Intrahepatic lipid content assessed by proton magnetic resonance spectroscopy at baseline and completion intestinal fructose tolerance after oral fructose in comparison to oral glucose hepatic fructose tolerance serum glucose and phosphate after oral fructose in comparison to healthy individuals and renal fructose tolerance urinary glucose phosphate pH and amino acids after oral fructose in comparison to healthy individuals Nature and extent
Recently PF-06835919 a KHK inhibitor KHKi was developed as a new treatment for non-alcoholic fatty liver disease The compound was well tolerated in several phase II clinical trials
It is hypothesized that PF-06835919 is also effective in patients with HFI Objective To study the effects of PF-06835919 on fructose tolerance and intrahepatic lipid content in patients with HFI Study design open-label pilot study Study population three adult patients with HFI will be treated with PF-06835919 Five adult healthy individuals will be included but not be treated as a reference Intervention if applicable Patients receive once daily in the morning three tablets of 100 mg PF-06835919 for 9 days They will subsequently be gradually exposed to increasing doses of either oral fructose or glucose in a blinded fashion Healthy individuals will only undergo oral fructose exposure as a reference Main study parametersendpoints Intrahepatic lipid content assessed by proton magnetic resonance spectroscopy at baseline and completion intestinal fructose tolerance after oral fructose in comparison to oral glucose hepatic fructose tolerance serum glucose and phosphate after oral fructose in comparison to healthy individuals and renal fructose tolerance urinary glucose phosphate pH and amino acids after oral fructose in comparison to healthy individuals Nature and extent
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None