Diagnosis and Treatment of Patients With Inborn Errors of Metabolism

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00369421
First received: August 25, 2006
Last updated: September 13, 2014
Last verified: September 2014
  Purpose

Researchers intend on diagnosing and treating certain inborn errors of metabolism. By doing this researchers hope to expand their knowledge about these disorders and provide access to patients of interest for research, teaching, and clinical experience.

Patients participating in this study will be examined and treated on an out patient basis, if practical. However, patients requiring specialized tests or treatments will be admitted to the NIH Clinical Center as necessary. Researchers will use only accepted medical procedures in diagnosing (medical history, physical examinations, X-ray studies, eye examinations, blood tests, and urine tests) and treating the patients involved in this study. Additional tests may be required on a case to case basis.

Many patients seen in this study will go on to be enrolled in a specific disease-related research study.< TAB>


Condition
Metabolism

Study Type: Observational
Official Title: Diagnosis and Treatment of Patients With Inborn Errors of Metabolism or Other Genetic Disorders

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 3000
Study Start Date: November 1976
Detailed Description:

We propose to characterize the etiology and natural history of rare inborn errors of metabolism and other genetic disorders, both known and yet-to-be discovered. In so doing, we will expand our knowledge about these disorders and provide access to patients of interest for research, teaching, and clinical experience. Individual patients seen under this protocol have prompted the establishment of specific disease-related protocols involving intensive natural history studies and innovative therapies. In addition to its longstanding role in investigating individuals who are of interest to the Section on Human Biochemical Genetics, this protocol provides one possible avenue (in addition to other NIH protocols) for admitting patients who are part of the NIH Undiagnosed Diseases Program.

  Eligibility

Ages Eligible for Study:   1 Month and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • Inclusion/Exclusion criteria

Patients enrolled in this protocol will have been referred with a known or suspected inborn error of metabolism, heritable disorder, or genetic predisposition. Examples include inherited developmental defects or diatheses toward infections, cancer, or an environmentally induced disease. The principal investigator, along with consulting specialists, will review the medical records of prospective subjects and offer admission based upon the potential to help the individual, to learn from the patient, or to initiate clinical or basic research suggested by the patient s workup. Prior to late 2008, patients enrolled in this protocol had disorders of current or potential future research interest to the Principal Investigator or an Associate Investigator. Approximately 400 such patients were enrolled over the course of 32 years.

Beginning in 2008, the protocol became one of the vehicles for admitting patients with a broader range of inborn errors of metabolism (e.g., those with immune defects, developmental disorders, cancer diatheses, etc.) through the NIH UDP. There are several aspects of this process:

  1. < TAB> Screening and triaging. Records are reviewed by the UDP Director for completeness and missing articles (e.g., images, biopsy slides) are requested. The UDP Director assigns records for review to consultants based upon the specialty involved, and copies of the records are distributed to 1-5 experts.
  2. < TAB> Criteria for eligibility. Eligibility criteria include novelty of clinical findings, multiple family members affected, or an objective laboratory or imaging clue to pursue. Of course, patients have to be able to travel, as well.
  3. < TAB> Roles of the UDP personnel. The UDP Director performs the triage, makes the final decision, and signs the decision letters. The consultants are NIH clinical specialists from the Clinical Center departments and the ICs. A group of nurse practitioners and one physician s assistant communicate about medical issues with patients and referring physicians. Support personnel obtain missing articles, copy records, file them, send out letters of receipt, enter information in the Lab Matrix database, and answer phone calls.
  4. < TAB> Consent timing and process. In general, consent is obtained by the care team upon admission. Occasionally, a patient or family member gives consent for a blood draw locally; this is obtained by an Associate Investigator over the phone and in writing.

Patients apply with a summary letter from their referring physician and with their medical records; the cases are then reviewed by members of a large group of NIH consultants. If any of those consultants finds that an applicant qualifies for her/his protocol (in any institute), the patient is invited to enroll in that protocol. The UDP connects the patient with the principal investigator; there is no involvement of protocol 76-HG-0238.

For patients not selected by other services, the UDP Director, based largely on specialists recommendations, makes the final decision regarding acceptance or rejection with respect to protocol 76-HG-0238. The UDP has evolved such that the majority of its patients are now being enrolled in 76-HG-0238.

Once a patient is enrolled in 76-HG-0238, her/his management is the same regardless of whether or not entry was through the UDP. Specifically, in each case, all testing except the skin biopsy, DNA analysis, and research bloods is medically indicated and directed toward diagnosis.

Some subjects will be relatives of patients with known diagnoses, and their specimens will be obtained for the purpose of heterozygote testing or to serve as controls to help diagnose the proband. All subjects shall be admitted as inpatients or outpatients at the discretion of the principal investigator, based upon particular research interests and expertise.

Individuals will be excluded from this protocol if they already have a diagnosis, if their previous evaluations leave no clue to pursue, if they appear to have a known diagnosis that has not been made, or if their subjective complaints far exceed any objective findings. We will not admit patients under one month of age to this protocol. This exclusion occurs because there is no urgency for a very early diagnosis and care is more readily proffered to older individuals at the Clinical Center. Patients under one year of age will be admitted only if they are medically stable and require admission to the Clinical Center for diagnosis.

Normal adult volunteers will be enrolled to provide control blood and urine specimens. NIH employees and members of their immediate families may participate in this protocol as normal volunteers. We will follow the Guidelines for the Inclusion of Employees in NIH Research Studies and will give each employee a copy of the NIH information sheet on Employee Research Participation.

For NIH employees:

  1. Neither participation nor refusal to participate will have an effect, either beneficial or adverse, on the participant s employment or work situation.
  2. The NIH information sheet regarding NIH employee research participation will be distributed to all potential subjects who are NIH employees.
  3. The employee subject s privacy and confidentiality will be preserved in accordance with NIH Clinical Center policies, which define the scope and limitations of the protections.
  4. For NIH employee subjects, consent will be obtained by an individual independent of the employee s team. Those in a supervisory position to any -12- employee and co-workers of the employee will not obtain consent.
  5. The importance of maintaining confidentiality when obtaining potentially sensitive and private information from co-workers or subordinates will bereviewed with the study staff at least annually and more often if warranted.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369421

Contacts
Contact: William A Gahl, M.D. (301) 402-2739 bgahl@helix.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: William A Gahl, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00369421     History of Changes
Other Study ID Numbers: 760238, 76-HG-0238
Study First Received: August 25, 2006
Last Updated: September 13, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Dietary Therapy
Biochemical Defects
Enzyme Defects
Transport
Rare Diseases
Varied Disorders
Screening
Relatives

Additional relevant MeSH terms:
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on September 18, 2014