PhenylketonuriaPhase 2NCT01395394

Phenylketonuria, Oxidative Stress, and BH4

A Phase 2 study testing Kuvan and Meal Challenge in people with Phenylketonuria, run by Emory University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to see how tetrahydrobiopterin therapy (BH4; also known as sapropterin dihydrochloride or Kuvan) affects measures of oxidative stress and endothelial function in patients with Phenylketonuria (PKU). Read more about this study

Who is it for?: Ages 10 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Phenylketonuria
What is being tested?: Kuvan and Meal Challenge
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: Jun 2011to Jun 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 10 to 45 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

Have read, understood, and signed this consent form (and assent form, if <18 years old)
Are between the ages of 10-45 years
Weigh at least 75 pounds (34 kg)
Meet group-specific criteria

Who cannot join

Smoke
Have any history of cardiovascular disease
Have hepatic impairment, or demonstrate abnormal baseline liver function lab test results
Have donated blood within 3 months prior to the study or are anemic as shown by the baseline lab results
Are unwilling to discontinue dietary supplements (excluding medical food) two weeks prior to their first study visit
Are currently take medications that will interfere with the interpretation of selected endpoints (such as lipid-lowering medication)

Show all 10Show fewer

Are currently pregnant or breastfeeding
Excluding PKU, have a chronic illness, disorder, or condition (including but not limited to diabetes, hypertension, cancer)
Have taken any investigational drug (including Kuvan for Kuvan-unresponsive participants \& controls) within 3 months prior to the study
In the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures

Trial locations and contacts

1 site in 1 country.

United States1 site

Emory University
Decatur, Georgia, 30033

Other trials in United States

About this study

Official title: The Ability of Kuvan® (Sapropterin Dihydrochloride) to Prevent Meal-induced Lipid Peroxidation and Endothelial Dysfunction in Patients With Phenylketonuria: a Pilot Study

Read the detailed description

Oxidative stress will be induced by having participants eat a meal in polyunsaturated fats. The investigators will see how participants respond to the meal challenge over the course of 6 hours.

PKU participants who are currently on BH4 therapy will be evaluated while taking BH4 with the meal at a single study visit.
PKU participants who did not responded to BH4 therapy will be evaluated twice. At the first study visit the investigators will see how you react to the meal challenge when you are not given BH4. You will be given BH4 for two weeks, then return for a second meal challenge study visit while taking BH4.
Healthy controls will be evaluated after consuming the meal only (no BH4) at a single study visit.

Conditions: Phenylketonuria
Being tested: Kuvan, Meal Challenge
Keywords: Phenylketonuria, PKU, tetrahydrobiopterin, sapropterin dihydrochloride, BH4, Kuvan, Oxidative stress
Medical subject headings: Phenylketonurias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KuvanDrug
Also called Sapropterin dihydrochloride, tetrahydrobiopterin, BH4
Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2.
Meal ChallengeOther
At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction

Study groups in NCT01395394
Study group	Role	What they receive
BH4 Non-Responders	Experimental	Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4. Receives: Drug: Kuvan; Other: Meal Challenge
Healthy Controls	Experimental	Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4. Receives: Other: Meal Challenge
BH4 Responders	Experimental	Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal. Receives: Other: Meal Challenge

What is being measured

The primary outcome is the main question the study is designed to answer.

Lipid Peroxidation
Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month.
Measured: Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups
C-Reactive Protein (CRP)
Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month.
Measured: CRP will be measured every other hour for six hours at baseline (study visit 1) for all study groups and again during a second visit 2 weeks after baseline in BH4 Non-Responders only (study visit 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2011Jun 2013

First posted15 Jul 2011 (estimated)
Study startJun 2011
Primary completionJun 2013
Study completionJun 2013

Why it stopped: Difficulty with recruitment and agreed with Sponsor to report completed data as case reports

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for PhenylketonuriaStudies of the same condition, open and under way.
More trials run by Emory 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 2
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01395394
Sponsor's protocol ID: IRB00046153
Status last verified: Aug 2014
First submitted: 23 Jun 2011
Last updated: 28 Aug 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
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RecruitingPhase 2
A Study of MZE782 in Adults With PKU
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RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
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Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria

All Phenylketonuria trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Ability of Kuvan® (Sapropterin Dihydrochloride) to Prevent Meal-induced Lipid Peroxidation and Endothelial Dysfunction in Patients With Phenylketonuria: a Pilot Study
ClinicalTrials.gov ID: NCT01395394
Acronym / sponsor ID: IRB00046153
Conditions: Phenylketonuria
Keywords: Phenylketonuria, PKU, tetrahydrobiopterin, sapropterin dihydrochloride, BH4, Kuvan, Oxidative stress
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Difficulty with recruitment and agreed with Sponsor to report completed data as case reports
Enrolment: 12 participants (actual)
Lead sponsor: Emory UniversityUniversity, hospital or other
Study start: Jun 2011
Primary completion: Jun 2013 (actual)
Study completion: Jun 2013 (actual)
First posted: 15 Jul 2011 (estimated)
Results: Posted 28 Aug 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Oxidative stress will be induced by having participants eat a meal in polyunsaturated fats. The investigators will see how participants respond to the meal challenge over the course of 6 hours.

PKU participants who are currently on BH4 therapy will be evaluated while taking BH4 with the meal at a single study visit.
PKU participants who did not responded to BH4 therapy will be evaluated twice. At the first study visit the investigators will see how you react to the meal challenge when you are not given BH4. You will be given BH4 for two weeks, then return for a second meal challenge study visit while taking BH4.
Healthy controls will be evaluated after consuming the meal only (no BH4) at a single study visit.

Study design

Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
BH4 Non-Responders	Experimental	Drug: Kuvan, Other: Meal ChallengeParticipants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4.
Healthy Controls	Experimental	Other: Meal ChallengeParticipants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4.
BH4 Responders	Experimental	Other: Meal ChallengeParticipants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal.

Who may qualify

Ages: 10 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

Have read, understood, and signed this consent form (and assent form, if <18 years old)
Are between the ages of 10-45 years
Weigh at least 75 pounds (34 kg)
Meet group-specific criteria

Key exclusion criteria (10 listed)

Smoke
Have any history of cardiovascular disease
Have hepatic impairment, or demonstrate abnormal baseline liver function lab test results
Have donated blood within 3 months prior to the study or are anemic as shown by the baseline lab results
Are unwilling to discontinue dietary supplements (excluding medical food) two weeks prior to their first study visit

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
KuvanAlso: Sapropterin dihydrochloride, tetrahydrobiopterin, BH4Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2.	Drug	BH4 Non-Responders
Meal ChallengeAt each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction	Other	BH4 Non-Responders, BH4 Responders, Healthy Controls

Primary outcome

Lipid Peroxidation
Time frame: Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups
Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month.
C-Reactive Protein (CRP)
Time frame: CRP will be measured every other hour for six hours at baseline (study visit 1) for all study groups and again during a second visit 2 weeks after baseline in BH4 Non-Responders only (study visit 2)
Markers will be assessed every other hour for each 6-hour study visit. Kuvan responders and healthy controls will only be assessed at one 6-hour study visit. Kuvan non-responders will be assessed at two study visits (a baseline visit, and a visit after two weeks of Kuvan therapy). Values will be assessed groupwise and also assessed for intrapersonal change in the Kuvan non-responsive group. Time frame of participation is estimated at one month.

Results and safety

Results posted to the registry on 28 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BH4 Non-Responders	4	3
Healthy Controls	3	3
BH4 Responders	5	5

Primary outcome: Lipid Peroxidation

Time frame: Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups. Mean (Standard Deviation). Unit: umole/L

Measure	BH4 Non-Responders n = 0	Healthy Controls n = 0	BH4 Responders n = 3
Baseline (prior to meal challenge)	–	–	0.57 (0.33)
2-hours post meal	–	–	0.62 (0.53)
4-hours post meal	–	–	0.73 (0.39)
6-hours post meal	–	–	0.78 (0.47)

Population analysed: Study was terminated due to difficulty recruiting patients, thus analysis was limited to preliminary data on 11 patients only. TBARS was measured in 3 BH4 responders only - data were unavailable for 8 other participants (2 responders, 3 non-responders, and 3 controls) due to inadequate sample volume.

Primary outcome: C-Reactive Protein (CRP)

Time frame: CRP will be measured every other hour for six hours at baseline (study visit 1) for all study groups and again during a second visit 2 weeks after baseline in BH4 Non-Responders only (study visit 2). Mean (Standard Deviation). Unit: mg/dl

Measure	BH4 Non-Responders n = 3	Healthy Controls n = 2	BH4 Responders n = 5
Baseline, prior to meal challenge (n=3, 2, 5)	1.46 (1.47)	0.61 (0.14)	1.04 (1.48)
2-hours post meal (n=3, 2, 5)	1.50 (1.49)	0.58 (0.12)	0.99 (1.40)
4-hours post meal (n=3, 2, 5)	1.55 (1.50)	0.55 (0.18)	0.96 (1.33)
6-hours post meal (n=3, 2, 5)	1.59 (1.60)	0.55 (0.11)	0.90 (1.24)
Baseline V2, prior to meal challenge (n=3, 0, 0)	1.51 (1.56)	NA (NA)	NA (NA)
2-hours post meal (V2; n=3, 0, 0)	1.55 (1.67)	NA (NA)	NA (NA)
4-hours post meal (V2; n=3, 0, 0)	1.79 (2.11)	NA (NA)	NA (NA)
6-hours post meal (V2; n=3, 0, 0)	1.58 (1.69)	NA (NA)	NA (NA)

Population analysed: Study was terminated due to difficulty recruiting patients, thus analysis was limited to preliminary data on 11 patients only. CRP was measured in 10 subjects - data were unavailable for 1 control participant due to inadequate sample volume.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BH4 Non-Responders	0 of 4 (0%)	0 of 4 (0%)	Not reported
Healthy Controls	0 of 3 (0%)	0 of 3 (0%)	Not reported
BH4 Responders	0 of 5 (0%)	0 of 5 (0%)	Not reported

Limitations and caveats (from the sponsor): Early termination leading to small number of subjects analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Study WebsiteLink provided by the sponsor.

Related trials for Phenylketonuria

RecruitingPhase 1
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
Phenylketonuria
RecruitingPhase 2
A Study of MZE782 in Adults With PKU
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RecruitingPhase 3
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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.

Rani H Singh, PhD principal investigator

Emory University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Kuvan and Meal Challenge in people with Phenylketonuria, run by Emory University at 1 site in United States.

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 4 inclusion and 10 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: stopped early, as of the sponsor's last update on 28 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Lipid Peroxidation (time frame: Lipid peroxidation will be measured every other hour for six hours at baseline (study visit 1) for all study groups). 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 NCT01395394.

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 28 Aug 2014.