Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Biomarker for Wolman Disease (BioWolman) (BioWolman)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02383641
Recruitment Status : Recruiting
First Posted : March 9, 2015
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Centogene AG Rostock

Brief Summary:
Development of a new MS-based biomarker for the early and sensitive diagnosis of Wolman disease blood (plasma)

Condition or disease
Acid Lipase Deficiency Acid Cholesteryl Ester Hydrolase Deficiency, Wolman Type Cholesterol Ester Storage Disease

Detailed Description:

Wolman disease (WD) is a rare genetic disorder characterized by complete absence of an enzyme known as lysosomal acid lipase (LIPA). This enzyme is required to breakdown (metabolize) lipids in the body. Without the LIPA enzyme, lipids may abnormally accumulate in the tissues and organs of the body causing a variety of symptoms.

WD is the most severe expression of LIPA deficiency. Milder form of the disorder are known as cholesteryl ester storage deficiency. The symptoms of WD usually become apparent shortly after birth, usually during the first few weeks of life. Affected infants may develop bloating or abdominal distention and may have significant hepatosplenomegaly. Fibrosis of the liver may also occur. In some cases, fluid may accumulate in the abdominal cavity (ascites). Infants with WD have serious digestive abnormalities including malabsorption, a condition in which the intestines fail to absorb nutrients and calories from food. Malabsorption associated with WD causes persistent and often forceful vomiting, frequent diarrhea, foul-smelling, fatty stools (steatorrhea) and malnutrition. Because of these digestive complications, affected infants usually fail to grow and gain weight at the expected rate for their age and sex (failure to thrive).

Hepatosplenomegaly and protrusion of the abdomen can cause umbilical hernia, a condition in which the contents of the stomach may push through an abnormal opening or tear in the abdominal wall near the bellybutton. Additional symptoms may also occur in WD including yellowing of the skin, mucous membranes and whites of the eyes (jaundice), a persistent low-grade fever, and poor muscle tone (hypotonia). Infants may exhibit delays in the development of motor skills.

A distinct finding associated with WD is the hardening of adrenal gland tissue due to the accumulation of calcium (calcification). The adrenal glands are located on top of the kidneys and produce epinephrine and norepinephrine. Other hormones produced by the adrenal glands help to regulate the fluid and electrolyte balance in the body. Calcification of the adrenal glands is not detectable by physical examination, but can be seen with x-ray study. Calcification may prevent the adrenal glands from producing enough essential hormones and can affect metabolism, blood pressure, the immune system and other vital processes of the body.

Infants with WD may experience the loss of previously acquired skills required the coordination of muscle and motor skills (psychomotor regression). The symptoms of WD often get progressively worse eventually leading to life-threatening complications during infancy including extremely low levels of circulating red blood cells (severe anemia), hepatic dysfunction or failure, and physical wasting away and severe weakness often associated with chronic disease and marked by weight loss and loss of muscle mass (cachexia or inanition).

WD is caused by mutations of the lysosomal acid lipase (LIPA) gene. It is inherited as an autosomal recessive trait. More than 50 cases have been reported in the medical literature. However, cases may go undiagnosed or misdiagnosed making it difficult to determine the disorder's true frequency in the general population.

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

Therefore it is the goal of the study to identify and validate a new biochemical marker from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.


Layout table for study information
Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Wolman Disease, AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL
Actual Study Start Date : August 20, 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021


Group/Cohort
Observation
Patients with Wolman disease or high-grade suspicion for Wolman disease



Primary Outcome Measures :
  1. Development of a new MS-based biomarker for the early and sensitive diagnosis of Wolman disease from blood [ Time Frame: 24 months ]
    New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.


Secondary Outcome Measures :
  1. Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 36 month ]
    the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.


Biospecimen Retention:   Samples With DNA
For the development of the new biomarkers using the technique of Mass-spectometry, maximal 7,5 ml blood will be taken from the patient via using a dry blood spot filter card. To prove the correct Wolman disease diagnosis in those patients where up to the enrolment in the study no genetic testing has been done, sequencing of Wolman disease will be done. The analyses will be done at the Centogene AG Am Strande 7 18055 Rostock Germany


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Wolman disease or high-grade suspicion for Wolman disease
Criteria

Inclusion Criteria:

  • Informed consent will be obtained from the parents before any study related procedures.
  • Patients of both gender older than 2 month
  • The patient has a diagnosis of Wolman disease or a high-grade suspicion for Wolman disease

High-grade suspicion present, if one or more inclusion criteria are valid:

  • Positive family anamnesis for Wolman disease
  • Vomiting, diarrhea
  • Malnourishment, difficulty growing and gaining weight
  • Enlarged liver and spleen (hepatosplenomegaly), which causes a distended abdomen
  • Low muscle tone (hypotonia)
  • Anemia
  • x-ray reveals calcified adrenal glands

Exclusion Criteria:

  • No Informed consent from the parents before any study related procedures.
  • Patients of both gender younger than 2 month
  • No diagnosis of Wolman disease or no valid criteria for profound suspicion of Wolman disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02383641


Contacts
Layout table for location contacts
Contact: Arndt Rolfs, Prof +4938180113500 ext 500 arndt.rolfs@centogene.com

Locations
Layout table for location information
Egypt
Children Hospital, Faculty of Medicine, Cairo University Recruiting
Cairo, Egypt, 11511
Contact: Laila Selim, Prof.         
Germany
Centogene AG Active, not recruiting
Rostock, Germany, 18055
India
Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN) Recruiting
Mumbai, India, 400705
Contact: Anil Jalan, Dr.         
Sponsors and Collaborators
Centogene AG Rostock
Investigators
Layout table for investigator information
Principal Investigator: Arndt Rolfs, Prof. Centogene AG Rostock

Additional Information:
Layout table for additonal information
Responsible Party: Centogene AG Rostock
ClinicalTrials.gov Identifier: NCT02383641     History of Changes
Other Study ID Numbers: BWD 06-2018
First Posted: March 9, 2015    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centogene AG Rostock:
Wolman disease
Biomarker
Additional relevant MeSH terms:
Layout table for MeSH terms
Wolman Disease
Cholesterol Ester Storage Disease
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Metabolic Diseases