Ignite Creation Date:
2024-05-06 @ 8:12 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06299891
Status:
RECRUITING
Last Update Posted:
2024-04-16
First Post:
2024-03-01
Brief Title:
Efficacy and Safety of PhentermineTopiramate in Youth With Hypothalamic Obesity
Sponsor:
Seattle Childrens Hospital
Organization:
Seattle Childrens Hospital
Study Overview
Official Title:
PhentermineTopiramate in Children Adolescents and Young Adults With Hypothalamic Obesity a Pilot and Feasibility Study
Status:
RECRUITING
Status Verified Date:
2024-07
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:
None
Brief Summary:
Hypothalamic obesity HO refers to the substantial weight gain that often complicates hypothalamic brain tumors Children with this treatment-recalcitrant form of obesity have excess rates of metabolic sequelae compared to otherwise healthy children with similar obesity and later experience excess mortality related to cardiometabolic disease In this pilot trial our objective is to gather key preliminary data about phenterminetopiramate PhT that is FDA-approved for common obesity but has never been tested in HO The subset of individuals with HO who experience hyperphagia or excess daytime sleepiness may benefit from the PhT-induced decrease in appetite and increase in alertness
Preliminary assessments of safety adverse events dosing Aim 1 as well as of efficacy BMI loss Aim 2 will be made in a 28-week parallel-arm double-blinded Phase 2 placebo-controlled clinical trial in 12-28-year-old individuals with HO
Preliminary assessments of safety adverse events dosing Aim 1 as well as of efficacy BMI loss Aim 2 will be made in a 28-week parallel-arm double-blinded Phase 2 placebo-controlled clinical trial in 12-28-year-old individuals with HO
Detailed Description:
STUDY OVERVIEW This is a two-center double-blind participant and assessor randomized parallel-arm 28-week clinical phase II trial comparing changes from pre- to post treatment in two study arms of active drug Qsymia vs placebo capsules Twenty-four 12-28-year-old participants will be randomized 11 into the two intervention groups The study will have a single central IRB CHOP
In this pilot trial the objective is to gather key preliminary data about phenterminetopiramate PhT a promising option containing a sympathomimetic amine Ph combined with an appetite-suppressive epilepsy drug T that is FDA-approved for common obesity but has never been tested in HO The subset of individuals with HO who experience hyperphagia or excess daytime sleepiness may benefit from the PhT-induced decrease in appetite and increase in alertness Preliminary assessments of safety and dosing adverse events and maximum tolerated dose - Aim 1 as well as of efficacy BMI loss - Aim 2 will be made in a 28-week parallel-arm double-blinded Phase 2 randomized placebo-controlled clinical trial in 12-28-year-old individuals with HO The FDA-approved dose titration will be followed Other efficacy and mechanistic outcomes will be measured as well
Specific Aims
Aim 1 To assess safety and maximum tolerated dose of PhT Main outcomes treatment-emergent adverse events including any during withdrawal maximum tolerated dose weeks 0 to 28
Aim 2 To estimate the treatment effect of PhT with respect to weight loss in individuals with HO Main outcome change in BMI week 0 to 28 in response to PhT vs placebo
Study Approach
Recruitment Subjects will be required to travel to one of the two research sites Seattle WA Philadelphia PA Each subject will be treated for 28 weeks plus 1 week of an appropriate taper in those participants who reached the highest dose at titration
Participants will be pre-screened for eligibility via medical record review Once written informed consent is obtained eligibility will be confirmed
Randomization Eligible subjects will be assigned treatment using a permuted-block randomization 11 to drug vs placebo for 28 weeks with varying block sizes constructed by the CHOP study statistician
Study visits Each participant will have a screening visit and 5 in-person study visits Weeks 1 baseline 3 14 16 28 end of randomized trial There will be a remote contact one week - 3 days after dose initiation andor dose escalation to assess dose tolerability The remote contact at 29 weeks will be performed to assess for any withdrawal effects and will be done in-person if there are any safety concerns that are most appropriately assessed in person Visits at 1 and 28 weeks will be used for main outcome collection Interim visits are required for assessment of dose escalation Weeks 3 and 16 visits could be done remotely to reduce burden in particular for individuals traveling from a distance if participants prefer and have no concerning safety signals Participants will be compensated for their time and travel Efforts will be made to schedule study appointments at times that will accommodate participants schedules
Main outcome for Aim 1 Safety as assessed by systematic collection of treatment-emergent adverse events using a safety monitoring uniform report form SMURF with adverse events graded according to Common Terminology Criteria for Adverse Events CTCAE version 50
Secondary outcome for Aim 1 Maximum tolerated dose of PhT as defined by the dose of PhT that the participant is continuing to take at the week 28 visit reflecting any dose individualization
Main outcome for Aim 2 change in BMI between weeks 1 baseline and week 28 end of treatment
Key secondary outcomes for Aim 2 all assessed as change between weeks 1 and 28 proportion of participants who achieve at least 25 BMI reduction proportion of participants who achieve at least 5 BMI reduction change in fat mass and visceral fat as assessed by DXA from Baseline to Week 28
In this pilot trial the objective is to gather key preliminary data about phenterminetopiramate PhT a promising option containing a sympathomimetic amine Ph combined with an appetite-suppressive epilepsy drug T that is FDA-approved for common obesity but has never been tested in HO The subset of individuals with HO who experience hyperphagia or excess daytime sleepiness may benefit from the PhT-induced decrease in appetite and increase in alertness Preliminary assessments of safety and dosing adverse events and maximum tolerated dose - Aim 1 as well as of efficacy BMI loss - Aim 2 will be made in a 28-week parallel-arm double-blinded Phase 2 randomized placebo-controlled clinical trial in 12-28-year-old individuals with HO The FDA-approved dose titration will be followed Other efficacy and mechanistic outcomes will be measured as well
Specific Aims
Aim 1 To assess safety and maximum tolerated dose of PhT Main outcomes treatment-emergent adverse events including any during withdrawal maximum tolerated dose weeks 0 to 28
Aim 2 To estimate the treatment effect of PhT with respect to weight loss in individuals with HO Main outcome change in BMI week 0 to 28 in response to PhT vs placebo
Study Approach
Recruitment Subjects will be required to travel to one of the two research sites Seattle WA Philadelphia PA Each subject will be treated for 28 weeks plus 1 week of an appropriate taper in those participants who reached the highest dose at titration
Participants will be pre-screened for eligibility via medical record review Once written informed consent is obtained eligibility will be confirmed
Randomization Eligible subjects will be assigned treatment using a permuted-block randomization 11 to drug vs placebo for 28 weeks with varying block sizes constructed by the CHOP study statistician
Study visits Each participant will have a screening visit and 5 in-person study visits Weeks 1 baseline 3 14 16 28 end of randomized trial There will be a remote contact one week - 3 days after dose initiation andor dose escalation to assess dose tolerability The remote contact at 29 weeks will be performed to assess for any withdrawal effects and will be done in-person if there are any safety concerns that are most appropriately assessed in person Visits at 1 and 28 weeks will be used for main outcome collection Interim visits are required for assessment of dose escalation Weeks 3 and 16 visits could be done remotely to reduce burden in particular for individuals traveling from a distance if participants prefer and have no concerning safety signals Participants will be compensated for their time and travel Efforts will be made to schedule study appointments at times that will accommodate participants schedules
Main outcome for Aim 1 Safety as assessed by systematic collection of treatment-emergent adverse events using a safety monitoring uniform report form SMURF with adverse events graded according to Common Terminology Criteria for Adverse Events CTCAE version 50
Secondary outcome for Aim 1 Maximum tolerated dose of PhT as defined by the dose of PhT that the participant is continuing to take at the week 28 visit reflecting any dose individualization
Main outcome for Aim 2 change in BMI between weeks 1 baseline and week 28 end of treatment
Key secondary outcomes for Aim 2 all assessed as change between weeks 1 and 28 proportion of participants who achieve at least 25 BMI reduction proportion of participants who achieve at least 5 BMI reduction change in fat mass and visceral fat as assessed by DXA from Baseline to Week 28
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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