HypophosphatasiaNCT04925804
Unraveling Genetics of HypoPhosPhatasia (HPP Genetics)
An observational study of Hypophosphatasia, run by CENTOGENE GmbH Rostock at 1 site in Germany.
Trial summary
Observational study to perform Whole Genome Sequencing in participants clinically suspected for HPP and negative for known pathogenic ALPL variants Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypophosphatasia
- How many people
- 16 participants
- Where
- 1 siteGermany
- Study dates
- 2 Jun 2021to 2 Dec 2021
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The participant is clinically suspected for HPP with no pathogenic variant/s in the ALPL gene
- Informed consent is obtained from the participant or from the parent / legal guardian
- The participant is clinically suspected for HPP
- The participant does not have pathogenic variant/s in the ALPL gene
- The participant showed low alkaline phosphatase levels (age- and sex-adjusted) on at least two occasions at least a month apart based on the local laboratory reference range
- None of these conditions are present:
- Celiac disease and
- Clofibrate therapy and
- Cleidocranial dysplasia and
- Cushing's syndrome and
- Hypothyroidism and
- Massive Blood transfusion and
- Milk-alkali syndrome and
- Multiple myeloma and
- Osteogenesis imperfecta, type II and
- Pernicious or profound anemia and
- Starvation and
- Vitamin C deficiency and
- Vitamin D intoxication and
- Zinc deficiency and
- Magnesium deficiency
Trial locations and contacts
1 site in 1 country.
Germany1 site
Universität Würzburg - Klinische Studieneinheit, Orthopädische Klinik
Würzburg, 97074
About this study
Official title: Unraveling Genetics of HypoPhosPhatasia (HPP Genetics) Observational Study
Observational study to perform Whole Genome Sequencing in participants clinically suspected for HPP and negative for known pathogenic ALPL variants
Read the detailed description
Hypophosphatasia (HPP) is a rare Inborn Error of Metabolism (IEM), characterized by low tissue-nonspecific isoenzyme of alkaline phosphatase (ALP) activity. Alkaline phosphatase (ALP) is crucial for osteoid mineralization. Its main substrate in bone is pyrophosphate (PPi), a natural inhibitor of mineralization. ALP cleaves pyrophosphate into its two phosphate moieties, which then become available to the mineralization process. This ALP deficiency results in accumulation of its substrates, mainly inorganic pyrophosphate (PPi), pyridoxal-5-phosphate (PLP), and phosphoethanolamine (PEA).
Beyond the bone and the Central Nervous System (CNS), ALP deficiency has an impact on a number of other organs and systems, resulting in a broad range of manifestations, including dental (premature tooth loss), muscular (muscle weakness, delayed walking, abnormal gait), rheumatic (calcium pyrophosphate deposition disease, fibromyalgia, fatigue, joint laxity), eye (calcifications), renal (nephrocalcinosis, kidney stones, renal failure), and gastrointestinal tract disturbance (gastroesophageal reflux).
The specific symptoms can vary greatly from one person to another, sometimes even among members of the same family. There are five major clinical forms of HPP (perinatal, infantile, childhood, adult, and odontohypophosphatasia), ranging from an extremely severe form that can cause stillbirth to a form associated with only premature loss of baby (deciduous) teeth, but no bone abnormalities.
The genetic reason of Hypophosphatasia is mainly caused by mutations in the ALPL gene, coding for the tissue nonspecific alkaline phosphatase isoenzyme. At least 397 distinct pathogenic variants (predominantly missense variants) were described to lead to low levels of the ALP enzyme. HPP can be inherited in an autosomal recessive (most perinatal and infantile forms) or autosomal dominant manner (typically the adult form and odontohypophosphatasia).
Since ALPL dependent prevalence is very low, while symptoms overlapping HPP are much more common, other primary - genetic - forms of HPP-like symptoms are to be sought and characterized.
The HPP genetics study aims to characterize the genetic background of HPP participants, who do not have pathogenic variant/s in the ALPL gene.
- Conditions
- Hypophosphatasia
- Keywords
- Hypophosphatasia, HPP, non-ALPL
- Medical subject headings
- Hypophosphatasia
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic analysis (WGS) of participants clinically suspected for HPP
Analyis of Whole Genome Sequencing data in participants clinically suspected for HPP disease to characterize the genetic background of these 16 HPP subjects, who do not have pathogenic variant/s in the ALPL gene.
Measured: 6 months
Secondary outcomes (1)
Analysis and identification of genetic variants
Identification and validation of genetic variants in the selected cohort (16 WGS subjects; see Outcome 1) since ALPL dependent prevalence is very low, while symptoms overlapping HPP are much more common, other primary - genetic - forms of HPP-like symptoms are to be sought and characterized.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2021
- Study start2 Jun 2021
- Primary completion2 Dec 2021
- Study completion2 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypophosphatasiaStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- CENTOGENE GmbH Rostock
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Peter Bauer, Prof. Dr., Study chair, CENTOGENE GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04925804
- Sponsor's protocol ID
- HPP genetics-2020
- Status last verified
- Dec 2021
- First submitted
- 9 Jun 2021
- Last updated
- 29 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is possible, but not determined, yet.
Publications
Seefried L, Petryk A, Del Angel G, Reder F, Bauer P. Whole genome sequencing in adults with clinical hallmarks of hypophosphatasia negative for ALPL variants. Mol Biol Rep. 2024 Sep 14;51(1):984. doi: 10.1007/s11033-024-09906-7.
PubMed 39276275
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unraveling Genetics of HypoPhosPhatasia (HPP Genetics) Observational Study
- ClinicalTrials.gov ID
- NCT04925804
- Acronym / sponsor ID
- HPP genetics-2020
- Conditions
- Hypophosphatasia
- Keywords
- Hypophosphatasia, HPP, non-ALPL
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- CENTOGENE GmbH RostockIndustry (pharma, biotech, devices)
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- 2 Jun 2021 (actual)
- Primary completion
- 2 Dec 2021 (actual)
- Study completion
- 2 Dec 2021 (actual)
- First posted
- 14 Jun 2021 (actual)
- 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.
Observational study to perform Whole Genome Sequencing in participants clinically suspected for HPP and negative for known pathogenic ALPL variants
Detailed description
Hypophosphatasia (HPP) is a rare Inborn Error of Metabolism (IEM), characterized by low tissue-nonspecific isoenzyme of alkaline phosphatase (ALP) activity. Alkaline phosphatase (ALP) is crucial for osteoid mineralization. Its main substrate in bone is pyrophosphate (PPi), a natural inhibitor of mineralization. ALP cleaves pyrophosphate into its two phosphate moieties, which then become available to the mineralization process. This ALP deficiency results in accumulation of its substrates, mainly inorganic pyrophosphate (PPi), pyridoxal-5-phosphate (PLP), and phosphoethanolamine (PEA).
Beyond the bone and the Central Nervous System (CNS), ALP deficiency has an impact on a number of other organs and systems, resulting in a broad range of manifestations, including dental (premature tooth loss), muscular (muscle weakness, delayed walking, abnormal gait), rheumatic (calcium pyrophosphate deposition disease, fibromyalgia, fatigue, joint laxity), eye (calcifications), renal (nephrocalcinosis, kidney stones, renal failure), and gastrointestinal tract disturbance (gastroesophageal reflux).
The specific symptoms can vary greatly from one person to another, sometimes even among members of the same family. There are five major clinical forms of HPP (perinatal, infantile, childhood, adult, and odontohypophosphatasia), ranging from an extremely severe form that can cause stillbirth to a form associated with only premature loss of baby (deciduous) teeth, but no bone abnormalities.
The genetic reason of Hypophosphatasia is mainly caused by mutations in the ALPL gene, coding for the tissue nonspecific alkaline phosphatase isoenzyme. At least 397 distinct pathogenic variants (predominantly missense variants) were described to lead to low levels of the ALP enzyme. HPP can be inherited in an autosomal recessive (most perinatal and infantile forms) or autosomal dominant manner (typically the adult form and odontohypophosphatasia).
Since ALPL dependent prevalence is very low, while symptoms overlapping HPP are much more common, other primary - genetic - forms of HPP-like symptoms are to be sought and characterized.
The HPP genetics study aims to characterize the genetic background of HPP participants, who do not have pathogenic variant/s in the ALPL gene.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The participant is clinically suspected for HPP with no pathogenic variant/s in the ALPL gene
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Genetic analysis (WGS) of participants clinically suspected for HPP
Time frame: 6 months
Analyis of Whole Genome Sequencing data in participants clinically suspected for HPP disease to characterize the genetic background of these 16 HPP subjects, who do not have pathogenic variant/s in the ALPL gene.
1 secondary outcome
Analysis and identification of genetic variants
Time frame: 6 months
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 29 Dec 2021.
- Derived from this study: PubMed 39276275Seefried L, Petryk A, Del Angel G, Reder F, Bauer P. Whole genome sequencing in adults with clinical hallmarks of hypophosphatasia negative for ALPL variants. Mol Biol Rep. 2024 Sep 14;51(1):984. doi: 10.1007/s11033-024-09906-7.
- Individual participant dataSharing planned: Undecided. It is possible, but not determined, yet.
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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.
Peter Bauer, Prof. Dr. study chair
CENTOGENE GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypophosphatasia, run by CENTOGENE GmbH Rostock at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2021. 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 Germany. 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.
What does the primary outcome measure?
Genetic analysis (WGS) of participants clinically suspected for HPP (time frame: 6 months). 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 NCT04925804, which also lists 1 linked publication.
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 29 Dec 2021; AzTrials last refreshed its copy on 8 Nov 2026.