Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy

• ClinicalTrials.gov Identifier: NCT00001813
• Recruitment Status: Recruiting
• First Posted: November 4, 1999
• Last Update Posted: December 4, 2020
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information

• First Submitted Date: November 3, 1999
• First Posted Date: November 4, 1999
• Last Update Posted Date: December 4, 2020
• Actual Study Start Date: May 10, 1999
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: December 16, 2017)

Identify patients with genetic diseases [ Time Frame: Up to 3 days ]

Proportion of patients with four rare genetic diseases; xeroderma pigmentosum (XP), Cockayne syndrome (CS), the XP/CS complex and trichothiodystrophy (TTD)

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: March 20, 2020)

• Diagnosis confirmation [ Time Frame: up to 3 days ]
  -To confirm suspected cases of XP, XP/CS, CS, TTD, XP/TTD and other overlap syndrome patients-by review of clinical records, by clinical examination and by laboratory testing-To document presence (or absence) of cancers (skin, eye, tongue, or internal) in XP, XP/CS, CS, TTD, XP/TTD and other overlap syndrome patients-To document atypical clinical features or unusual environmental exposures of patients with XP, XP/CS, CS, TTD, XP/TTD and other overlap syndromes
• Tissue collection [ Time Frame: up to 3 days ]
  obtain tissue (skin, blood, hair or buccal cells) from XP, XP/CS, CS, TTD, XP/TTD and other overlap syndromes patients, their first-degree relatives and healthy volunteers for establishment of cell cultures and for examination of DNA repair and genetic analysis
• identify molecular defects [ Time Frame: up to 3 days ]
  identify molecular defects in the DNA repair or other genes in cells from patients with XP, XP/CS, CS, TTD, XP/TTD and other overlap syndromes and to attempt to correlate the defects with the clinical features
• overall survival [ Time Frame: yearly ]
  follow the clinical course of selected patients with XP, CS, XP/CS, TTD, XP/TTD and other

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy
• Official Title: Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy
• Brief Summary: Four rare genetic diseases, xeroderma pigmentosum (XP), Cockayne syndrome (CS), the XP/CS complex and trichothiodystrophy (TTD) have defective DNA excision repair although only XP has increased cancer susceptibility. We plan to perform careful clinical examination of selected patients with XP, XP/CS, CS, or TTD and follow their clinical course. We will obtain tissue (skin, blood, hair, buccal swabs) for laboratory examination of DNA repair and for genetic analysis. We hope to be able to correlate these laboratory abnormalities with the clinical features to better understand the mechanism of cancer prevention by DNA repair. Patients will be offered counseling and education for cancer control.
• Detailed Description: Four rare genetic diseases, xeroderma pigmentosum (XP), Cockayne syndrome (CS), the XP/CS complex and trichothiodystrophy (TTD) have defective DNA excision repair although only XP has increased cancer susceptibility. We plan to perform careful clinical examination of selected patients with XP, XP/CS, CS, TTD, XP/TTD and other overlap syndromes to follow their clinical course. We will obtain tissue (skin, blood, hair, buccal cells) for laboratory examination of DNA repair and for genetic analysis. We hope to be able to correlate these laboratory abnormalities with the clinical features to better understand the mechanism of cancer prevention by DNA repair. Patients will be offered counseling and education for cancer control.
• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients will be sought by contacting professional organizations (such as the American Academy of Dermatology-XP Task Force), lay support groups (such as the XP Society and the Share and Care CS Support Network) or by direct referral.@@@Healthy volunteers or NIH staff will be recruited through the Program for Healthy Volunteers (CRVP@mail.cc.nih.gov), through the Patient Recruitment and Public Liaison Office (prpl@mail.cc.nih.gov), or as a self-referral through the clinicaltrials.gov web site (http://clinicaltrials.gov). Healthy volunteers may also be approached by a member of the LCBG, NCI regarding interest in participating on this protocol.

Condition

• Cockayne Syndrome
• Skin Neoplasms
• Xeroderma Pigmentosum
• Trichothiodystrophy
• Genodermatosis

• Intervention: Not Provided

Study Groups/Cohorts

• 1
  Patients with XP, XP/CS, CS, or TTD
• 2
  Family members of patients with XP, XP/CS, CS, or TTD
• 3
  Healthy Volunteers

Publications *

• Barrett SF, Robbins JH, Tarone RE, Kraemer KH. Evidence for defective repair of cyclobutane pyrimidine dimers with normal repair of other DNA photoproducts in a transcriptionally active gene transfected into Cockayne syndrome cells. Mutat Res. 1991 Nov;255(3):281-91.
• Boltshauser E, Yalcinkaya C, Wichmann W, Reutter F, Prader A, Valavanis A. MRI in Cockayne syndrome type I. Neuroradiology. 1989;31(3):276-7.
• Merideth M, Tamura D, Angra D, Khan SG, Ferrell J, Goldstein AM, DiGiovanna JJ, Kraemer KH. Reproductive Health in Xeroderma Pigmentosum: Features of Premature Aging. Obstet Gynecol. 2019 Oct;134(4):814-819. doi: 10.1097/AOG.0000000000003490.
• Atkinson EC, Thiara D, Tamura D, DiGiovanna JJ, Kraemer KH, Hadigan C. Growth and nutrition in children with trichothiodystrophy. J Pediatr Gastroenterol Nutr. 2014 Oct;59(4):458-64. doi: 10.1097/MPG.0000000000000458.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 7, 2020): 750
• Original Enrollment (submitted: June 23, 2005): 500
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

• INCLUSION CRITERIA:
• On referral, subjects will be considered for inclusion in the study:

If they have clinical documentation of typical features of XP, XP/CS, CS or TTD, XP/TTD or other overlap syndromes or

If they have laboratory documentation of defective DNA repair or

If they have some suggestive clinical features and are willing to participate in the study or

if they are first degree relatives or other family members of patients with XP, XP/CS, CS, TTD, XP/TTD or other overlap syndromes

if they are healthy volunteers of age 1 year and above (including NIH employees) willing to donate blood, skin, buccal cells, or hair. Healthy volunteer children will not have skin biopsies performed if they are age 12 years or younger.

-Patients or legally authorized representatives must provide informed consent.

EXCLUSION CRITERIA:

Inability or unwillingness to provide tissue (skin, blood, buccal cells or hair) for laboratory studies.

positive pregnancy test in healthy volunteers

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Deborah E Tamura, R.N.; (240) 760-7355; dt220a@nih.gov

Contact: Kenneth H Kraemer, M.D.; (240) 760-6139; kraemerk@mail.nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00001813
• Other Study ID Numbers: 990099; 99-C-0099
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
• Study Sponsor: National Cancer Institute (NCI)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kenneth H Kraemer, M.D.; National Cancer Institute (NCI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: December 2, 2020