PhenylketonuriaNCT00065299
Low Phenylalanine Diet for Mothers With Phenylketonuria (PKU)
A study testing Restricted phenylalanine diet in people with Phenylketonuria, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 3 sites in United States.
Trial summary
Phenylketonuria (PKU) is a rare genetic condition. If not treated, PKU can cause severe mental retardation. Women with PKU are advised to eat a special diet when pregnant to prevent mental retardation in their children. This study will evaluate the effects of that diet on the children of mothers with PKU. Read more about this study
- Who is it for?
- Ages 0 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- Restricted phenylalanine diet
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 572 participants
- Where
- 3 sitesUnited States
- Study dates
- May 1984to Apr 2000
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 0 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Live in community setting
- Become pregnant or give birth during the term of the investigation
- Identified early in pregnancy
- Dietary therapy instituted prior to conception whenever possible
- Diagnosis of PKU based on results of Phe challenge, or clear diagnostic evidence in medical record
- Blood Phe > 4 mg/dl
Show all 10Show fewer
- Intellectually able to understand and comply with the requirements of the Phe restricted diet, understand an informed consent, and adequately communicate with clinic personnel
- IQ > 70
- Heterozygous sisters to HPA women
- Matched control from maternity facility; pregnancy and offspring from a non-PKU female and a PKU male
Who cannot join
- Women with evidence of pterin defect
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Illinois at Chicago
Chicago, Illinois
University of Texas Medical Branch at Galveston
Galveston, Texas
University of Southern California School of Medicine
Los Angeles, California, 90027
About this study
Official title: Effects of Maternal Phenylketonuria (PKU) on Pregnancy Outcome
Phenylketonuria (PKU) is a rare genetic condition. If not treated, PKU can cause severe mental retardation. Women with PKU are advised to eat a special diet when pregnant to prevent mental retardation in their children. This study will evaluate the effects of that diet on the children of mothers with PKU.
Read the detailed description
PKU is an autosomal recessive trait caused by the absence of phenylalanine hydroxylase. Phenylalanine hydroxylase is an enzyme involved in the metabolism of phenylalanine (Phe). When phenylalanine hydroxylase is absent or defective, Phe levels rise and toxic Phe metabolites accumulate, causing central nervous system injury. PKU is a treatable disease. Affected individuals must adhere to a diet low in Phe during childhood. Women with PKU should also adhere to a low Phe diet before and during pregnancy to avoid fetal damage. The offspring of women with untreated maternal hyperphenylalaninemia (HPA) usually exhibit mental retardation, microcephaly, growth retardation, and other congenital anomalies. This study will examine the effect of a restricted Phe diet on reproductive outcome in women with maternal HPA.
Participants in this study will be women with HPA whose blood Phe values are persistently greater than 4 mg/dl. Those women with blood Phe values consistently greater than 8 mg/dl will be placed on a Phe restricted diet to maintain plasma Phe concentrations between 2 and 8 mg/dl. This level of control is practical and achievable. Due to a gradient of increasing Phe level from mother to fetus, levels in the latter would vary from 3.5 to 12 mg/dl; these levels are usually associated with normal outcomes. Women will be monitored throughout their pregnancy on obstetric, biochemical, and nutritional parameters. Women on the Phe restricted diet will be given enough Phe-limited protein, calories, vitamins, and minerals to maintain adequate nutritional status. Folate supplementation will be provided. If indicated clinically, tyrosine (Tyr) and supplemental trace metals will be prescribed.
A matching control sample of women and their offspring will be developed in collaboration with associated coordinating and collaborating centers. The offspring of both groups of mothers will be followed as long as the project permits. Those offspring born to mothers admitted to the project during the first 2 to 3 years of the study will be assessed on their intellectual ability and physical health, as well as academic achievement in school. Those admitted during the last 3 to 4 years of the study will be assessed on their intellectual ability and physical health, recognizing that limited data will be available for these offspring.
- Conditions
- Phenylketonuria
- Being tested
- Restricted phenylalanine diet
- Keywords
- Hyperphenylalaninemia, PKU, Maternal PKU, Pregnancy outcome, Phenylalanine restricted diet, Tyrosine supplementation, Maternal hyperphenylalanemia during pregnancy
- Medical subject headings
- Phenylketonurias, Phenylketonuria, Maternal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Restricted phenylalanine dietBehavioural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2003 (estimated)
- Study startMay 1984
- Study completionApr 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 572 participants
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Investigators
- Richard Koch, M.D., Principal investigator, University of Southern CaliforniaReuben Matalon, M.D., Principal investigator, University of Illinois ChicagoBobbye M. Rouse, M.D., Principal investigator, University of Texas at Galveston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00065299
- Sponsor's protocol ID
- NICHD-PKU
- Other IDs
- 1N01HD23148, 1N01HD23155, 1N01HD23156
- Status last verified
- May 2000
- First submitted
- 21 Jul 2003
- Last updated
- 24 Jun 2005
- Results posted
- No
Publications
Levy HL, Guldberg P, Guttler F, Hanley WB, Matalon R, Rouse BM, Trefz F, Azen C, Allred EN, de la Cruz F, Koch R. Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. Pediatr Res. 2001 May;49(5):636-42. doi: 10.1203/00006450-200105000-00005.
PubMed 11328945Koch R, Levy HL, Matalon R, Rouse B, Hanley WB, Trefz F, Azen C, Friedman EG, de la Cruz F, Guttler F, et al. The international collaborative study of maternal phenylketonuria: status report 1994. Acta Paediatr Suppl. 1994 Dec;407:111-9. doi: 10.1111/j.1651-2227.1994.tb13468.x.
PubMed 7766945Matalon R, Michals K, Azen C, Friedman E, Koch R, Rouse B, Hanley WB, de la Cruz F. Maternal PKU Collaborative Study: pregnancy outcome and postnatal head growth. J Inherit Metab Dis. 1994;17(3):353-5. doi: 10.1007/BF00711828. No abstract available.
PubMed 7807951Koch R, Levy HL, Matalon R, Rouse B, Hanley W, Azen C. The North American Collaborative Study of Maternal Phenylketonuria. Status report 1993. Am J Dis Child. 1993 Nov;147(11):1224-30. doi: 10.1001/archpedi.1993.02160350098015.
PubMed 8237918Koch R, Hanley W, Levy H, Matalon R, Rouse B, Dela Cruz F, Azen C, Gross Friedman E. A preliminary report of the collaborative study of maternal phenylketonuria in the United States and Canada. J Inherit Metab Dis. 1990;13(4):641-50. doi: 10.1007/BF01799519.
PubMed 2122127
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Maternal Phenylketonuria (PKU) on Pregnancy Outcome
- ClinicalTrials.gov ID
- NCT00065299
- Acronym / sponsor ID
- NICHD-PKU
- Conditions
- Phenylketonuria
- Keywords
- Hyperphenylalaninemia, PKU, Maternal PKU, Pregnancy outcome, Phenylalanine restricted diet, Tyrosine supplementation, Maternal hyperphenylalanemia during pregnancy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 572 participants
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- May 1984
- Study completion
- Apr 2000
- First posted
- 22 Jul 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phenylketonuria (PKU) is a rare genetic condition. If not treated, PKU can cause severe mental retardation. Women with PKU are advised to eat a special diet when pregnant to prevent mental retardation in their children. This study will evaluate the effects of that diet on the children of mothers with PKU.
Detailed description
PKU is an autosomal recessive trait caused by the absence of phenylalanine hydroxylase. Phenylalanine hydroxylase is an enzyme involved in the metabolism of phenylalanine (Phe). When phenylalanine hydroxylase is absent or defective, Phe levels rise and toxic Phe metabolites accumulate, causing central nervous system injury. PKU is a treatable disease. Affected individuals must adhere to a diet low in Phe during childhood. Women with PKU should also adhere to a low Phe diet before and during pregnancy to avoid fetal damage. The offspring of women with untreated maternal hyperphenylalaninemia (HPA) usually exhibit mental retardation, microcephaly, growth retardation, and other congenital anomalies. This study will examine the effect of a restricted Phe diet on reproductive outcome in women with maternal HPA.
Participants in this study will be women with HPA whose blood Phe values are persistently greater than 4 mg/dl. Those women with blood Phe values consistently greater than 8 mg/dl will be placed on a Phe restricted diet to maintain plasma Phe concentrations between 2 and 8 mg/dl. This level of control is practical and achievable. Due to a gradient of increasing Phe level from mother to fetus, levels in the latter would vary from 3.5 to 12 mg/dl; these levels are usually associated with normal outcomes. Women will be monitored throughout their pregnancy on obstetric, biochemical, and nutritional parameters. Women on the Phe restricted diet will be given enough Phe-limited protein, calories, vitamins, and minerals to maintain adequate nutritional status. Folate supplementation will be provided. If indicated clinically, tyrosine (Tyr) and supplemental trace metals will be prescribed.
A matching control sample of women and their offspring will be developed in collaboration with associated coordinating and collaborating centers. The offspring of both groups of mothers will be followed as long as the project permits. Those offspring born to mothers admitted to the project during the first 2 to 3 years of the study will be assessed on their intellectual ability and physical health, as well as academic achievement in school. Those admitted during the last 3 to 4 years of the study will be assessed on their intellectual ability and physical health, recognizing that limited data will be available for these offspring.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 0 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Live in community setting
- Become pregnant or give birth during the term of the investigation
- Identified early in pregnancy
- Dietary therapy instituted prior to conception whenever possible
- Diagnosis of PKU based on results of Phe challenge, or clear diagnostic evidence in medical record
Key exclusion criteria (1 listed)
- Women with evidence of pterin defect
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 |
|---|---|---|
| Restricted phenylalanine diet | Behavioural | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2005.
- Background: PubMed 11328945Levy HL, Guldberg P, Guttler F, Hanley WB, Matalon R, Rouse BM, Trefz F, Azen C, Allred EN, de la Cruz F, Koch R. Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. Pediatr Res. 2001 May;49(5):636-42. doi: 10.1203/00006450-200105000-00005.
- Background: PubMed 7766945Koch R, Levy HL, Matalon R, Rouse B, Hanley WB, Trefz F, Azen C, Friedman EG, de la Cruz F, Guttler F, et al. The international collaborative study of maternal phenylketonuria: status report 1994. Acta Paediatr Suppl. 1994 Dec;407:111-9. doi: 10.1111/j.1651-2227.1994.tb13468.x.
- Background: PubMed 7807951Matalon R, Michals K, Azen C, Friedman E, Koch R, Rouse B, Hanley WB, de la Cruz F. Maternal PKU Collaborative Study: pregnancy outcome and postnatal head growth. J Inherit Metab Dis. 1994;17(3):353-5. doi: 10.1007/BF00711828. No abstract available.
- Background: PubMed 8237918Koch R, Levy HL, Matalon R, Rouse B, Hanley W, Azen C. The North American Collaborative Study of Maternal Phenylketonuria. Status report 1993. Am J Dis Child. 1993 Nov;147(11):1224-30. doi: 10.1001/archpedi.1993.02160350098015.
- Background: PubMed 2122127Koch R, Hanley W, Levy H, Matalon R, Rouse B, Dela Cruz F, Azen C, Gross Friedman E. A preliminary report of the collaborative study of maternal phenylketonuria in the United States and Canada. J Inherit Metab Dis. 1990;13(4):641-50. doi: 10.1007/BF01799519.
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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.
Richard Koch, M.D. principal investigator
University of Southern California
Reuben Matalon, M.D. principal investigator
University of Illinois Chicago
Bobbye M. Rouse, M.D. principal investigator
University of Texas at Galveston
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Restricted phenylalanine diet in people with Phenylketonuria, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 3 sites 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 10 inclusion and 1 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: finished, as of the sponsor's last update on 24 Jun 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00065299, which also lists 5 linked publications.
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 24 Jun 2005.