Classical HomocystinuriaNCT06622577
The Effect of Dietary Management and Cysteine Supplementation on Growth Parameters and Biochemical Control for Pediatric Qatari Patients Affected with Classical B6 Non-responsive Homocystinuria.
A study testing Cysteine in people with Classical Homocystinuria, run by Hamad Medical Corporation at 1 site in Qatar.
Trial summary
Classical homocystinuria (HCU) is an autosomal recessive disorder caused by the deficiency of an enzyme cystathionine β-synthase (CβS) that affects the catabolic pathway of the amino acid methionine (Met) which leads to an accumulation of high levels of methionine and Homocysteine causing complications in the multi… Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Classical Homocystinuria
- What is being tested?
- Cysteine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteQatar
- Study dates
- 1 Dec 2024to 31 Aug 2025
- 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 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All the patients with a confirmed diagnosis of HCU by molecular and biochemical testing who are either diagnosed through NBS or LD who are following the diet
- Both male and female gender from birth to 18 years
- Participants depending on the age of inclusion who are willing to participate
Who cannot join
- ✔ Patients with Pyridoxine responsive- homocystinuria
- Patients who are solely on medication without any dietary intervention ✔ Non-Qatari Patients with a confirmed diagnosis of HCU
Trial locations and contacts
1 site in 1 country.
About this study
Classical homocystinuria (HCU) is an autosomal recessive disorder caused by the deficiency of an enzyme cystathionine β-synthase (CβS) that affects the catabolic pathway of the amino acid methionine (Met) which leads to an accumulation of high levels of methionine and Homocysteine causing complications in the multi system. Therefore, a strict dietary management is crucial to maintain good biochemical control, growth parameters and avoid complications. The main objective would be to analyze the impact of the Met restricted diet on growth parameters, biochemical markers and long-term complications in patients up to 18 years. In addition, the efficacy of dietary management with additional cysteine (Cys) supplementation for the patients up to 18 years would also be examined.
The participants of the study would be recruited from the metabolic and genetics clinic in Hamad General Hospital (HGH), Qatar. All Qatari participants with confirmed diagnosis of HCU \<18 years of age will be included in the study. A mixed method study design would be used which include a cross sectional study design to assess the impact of methionine restricted diet on outcome variables and a single arm interventional study to analyze the effect of additional cysteine supplementation in patients from birth to 18 years. For the retrospective study, all the required data would be retrieved from electronic record from the Cerner of HMC and would be stored in a local drive with password protection. Further, all the eligible participants would be prospectively followed to supplement additional cysteine for the period of 6 months.
The collected data will be statistically analyzed using the "SPSS windows version 22.0 software. The study would improve better understanding of dietary management through the identified outcomes. The outcome of Cys supplementation will improve the protein tolerance, biochemical parameters, growth parameters and may standardize the Cys supplementation.
Read the detailed description
This single-arm interventional study aims to evaluate the efficacy of dietary management combined with additional cysteine (Cys) supplementation in patients with Classical Homocystinuria (HCU). The study will assess the impact on biochemical markers and growth parameters over a six-month period. The study will include pediatric patients from birth to 18 years old, residing in Qatar, a region with the highest global prevalence of HCU.
Classical HCU is an autosomal recessive disorder resulting from a deficiency in cystathionine β-synthase (CβS). This enzymatic deficiency disrupts the metabolism of methionine (Met) and leads to elevated levels of homocysteine (Hcy), while cysteine (Cys) levels remain low. Untreated, HCU can cause significant complications including ectopic lentis, elongated bones, intellectual disability, and thromboembolism. Management primarily involves dietary restrictions to reduce Met intake and supplementation of Cys, along with other treatments.
More research is needed to determine the appropriate cysteine levels in treated patients and whether additional L-cystine supplementation can improve outcomes in those with Classical homocystinuria.
In CBS deficiency, the formation of cysteine from methionine is disrupted, making cysteine a \"conditionally essential\" amino acid. Low cysteine concentrations may contribute to the disease\'s pathogenesis.
The Relationship Between Cysteine and Homocysteine (Hcy) is both cysteine and homocysteine (Hcy) contain thiol groups, and they exist in different reduced and oxidized forms. When Hcy levels are very high, they reduce the concentration of plasma cysteine, likely due to the limited thiol-binding capacity of plasma proteins. Improving homocysteine control by increasing cysteine levels highlights the importance of focusing on cysteine supplementation. Case reports even suggest that cysteine deficiency may lead to poor weight gain and growth, even with adequate energy intake.
Cysteine is added to most methionine-free L-amino acid supplements, but the quantities may not always be sufficient. Administering cysteine can be challenging due to its poor solubility and unpleasant taste.
This provides insight into the complexities of managing CBS deficiency and the potential need for individualized cysteine supplementation.
Despite the known benefits of dietary management, there is limited research on the impact of additional Cysteine supplementation. This study seeks to explore this aspect more comprehensively, especially considering varying practices and guidelines globally.
- Conditions
- Classical Homocystinuria
- Being tested
- Cysteine
- Keywords
- Methionine, Homocystinuria, cysteine
- Medical subject headings
- Homocystinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CysteineDietary supplement
Also called single arm interventional study
Cysteine supplementation would be given according to the 2001 ROSS guidelines for the HCU. Cys amino acid supplements are available in the form of powder, each sachet containing 4gm which provides 500mg of Cys per sachet that is available in HMC medical store from where patients receive the medical formula and food at free of cost. The dosage of cysteine will be calculated according to the weight of the patient with the age specific recommendation and prescribed by the metabolic dietitian which will be approved by the metabolic physician prior to the supply of cysteine supplements to the patients. It is not known to have any serious adverse events that is life threatening. A single arm interventional study is opted as the intervention involves all the participants without withholding the treatment. Moreover, a single arm interventional study on cysteine supplementation aims to provide evidence on its efficacy contributing to the advancement of clinical practice in HCU management.
| Study group | Role | What they receive |
|---|---|---|
| dietary management with additional Cysteine supplementation | Experimental | Not described Receives: Dietary Supplement: Cysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
improvement of the biochemical parameters specifically homocysteine and methionine levels
Biochemical Parameters:
Description: The primary outcome will assess the improvement in biochemical parameters, specifically homocysteine (umol/l) and methionine levels(umol/l), in patients with Homocystinuria (HCU) following Cysteine(Cys) supplementation.
Measurement Tool:
Blood tests will be used to measure the levels of homocysteine and methionine.
Measured: Six months
Secondary outcomes (1)
Improvement of growth parameters including weight, Height and BMI
Growth Parameters:
Description: The secondary outcome will evaluate changes in growth parameters, including weight, height, and Body Mass Index (BMI), to understand the impact of Cys supplementation on physical growth.
Weight Measurement:
Measurement Tool: Standard clinical scales. Unit of Measure: Kilograms (kg)
Height Measurement:
Measurement Tool: Stadiometer or measuring tape. Unit of Measure: Centimeters (cm)
BMI Calculation:
Calculation: BMI will be calculated using the formula: weight (kg) / height (m²).Unit of Measure: Kilograms per square meter (kg/m²)
Measured: six month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2024
- Study start1 Dec 2024 (estimated)
- Primary completion1 Jul 2025 (estimated)
- Study completion31 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Classical HomocystinuriaStudies of the same condition, open and under way.
- More trials run by Hamad Medical CorporationThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamad Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06622577
- Sponsor's protocol ID
- MRC-01-23-734
- Status last verified
- Jul 2024
- First submitted
- 26 Jul 2024
- Last updated
- 2 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The country has strict laws preventing sharing of IPD to any third party.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dietary Management and Cysteine Supplementation on Growth Parameters and Biochemical Control for Pediatric Qatari Patients Affected with Classical B6 Non-responsive Homocystinuria.
- ClinicalTrials.gov ID
- NCT06622577
- Acronym / sponsor ID
- MRC-01-23-734
- Conditions
- Classical Homocystinuria
- Keywords
- Methionine, Homocystinuria, cysteine
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Hamad Medical CorporationIndustry (pharma, biotech, devices)
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 31 Aug 2025 (estimated)
- First posted
- 2 Oct 2024 (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.
Classical homocystinuria (HCU) is an autosomal recessive disorder caused by the deficiency of an enzyme cystathionine β-synthase (CβS) that affects the catabolic pathway of the amino acid methionine (Met) which leads to an accumulation of high levels of methionine and Homocysteine causing complications in the multi system. Therefore, a strict dietary management is crucial to maintain good biochemical control, growth parameters and avoid complications. The main objective would be to analyze the impact of the Met restricted diet on growth parameters, biochemical markers and long-term complications in patients up to 18 years. In addition, the efficacy of dietary management with additional cysteine (Cys) supplementation for the patients up to 18 years would also be examined.
The participants of the study would be recruited from the metabolic and genetics clinic in Hamad General Hospital (HGH), Qatar. All Qatari participants with confirmed diagnosis of HCU \<18 years of age will be included in the study. A mixed method study design would be used which include a cross sectional study design to assess the impact of methionine restricted diet on outcome variables and a single arm interventional study to analyze the effect of additional cysteine supplementation in patients from birth to 18 years. For the retrospective study, all the required data would be retrieved from electronic record from the Cerner of HMC and would be stored in a local drive with password protection. Further, all the eligible participants would be prospectively followed to supplement additional cysteine for the period of 6 months.
The collected data will be statistically analyzed using the "SPSS windows version 22.0 software. The study would improve better understanding of dietary management through the identified outcomes. The outcome of Cys supplementation will improve the protein tolerance, biochemical parameters, growth parameters and may standardize the Cys supplementation.
Detailed description
This single-arm interventional study aims to evaluate the efficacy of dietary management combined with additional cysteine (Cys) supplementation in patients with Classical Homocystinuria (HCU). The study will assess the impact on biochemical markers and growth parameters over a six-month period. The study will include pediatric patients from birth to 18 years old, residing in Qatar, a region with the highest global prevalence of HCU.
Classical HCU is an autosomal recessive disorder resulting from a deficiency in cystathionine β-synthase (CβS). This enzymatic deficiency disrupts the metabolism of methionine (Met) and leads to elevated levels of homocysteine (Hcy), while cysteine (Cys) levels remain low. Untreated, HCU can cause significant complications including ectopic lentis, elongated bones, intellectual disability, and thromboembolism. Management primarily involves dietary restrictions to reduce Met intake and supplementation of Cys, along with other treatments.
More research is needed to determine the appropriate cysteine levels in treated patients and whether additional L-cystine supplementation can improve outcomes in those with Classical homocystinuria.
In CBS deficiency, the formation of cysteine from methionine is disrupted, making cysteine a \"conditionally essential\" amino acid. Low cysteine concentrations may contribute to the disease\'s pathogenesis.
The Relationship Between Cysteine and Homocysteine (Hcy) is both cysteine and homocysteine (Hcy) contain thiol groups, and they exist in different reduced and oxidized forms. When Hcy levels are very high, they reduce the concentration of plasma cysteine, likely due to the limited thiol-binding capacity of plasma proteins. Improving homocysteine control by increasing cysteine levels highlights the importance of focusing on cysteine supplementation. Case reports even suggest that cysteine deficiency may lead to poor weight gain and growth, even with adequate energy intake.
Cysteine is added to most methionine-free L-amino acid supplements, but the quantities may not always be sufficient. Administering cysteine can be challenging due to its poor solubility and unpleasant taste.
This provides insight into the complexities of managing CBS deficiency and the potential need for individualized cysteine supplementation.
Despite the known benefits of dietary management, there is limited research on the impact of additional Cysteine supplementation. This study seeks to explore this aspect more comprehensively, especially considering varying practices and guidelines globally.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dietary management with additional Cysteine supplementation | Experimental | Dietary Supplement: Cysteine |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- All the patients with a confirmed diagnosis of HCU by molecular and biochemical testing who are either diagnosed through NBS or LD who are following the diet
Key exclusion criteria (2 listed)
- ✔ Patients with Pyridoxine responsive- homocystinuria
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 |
|---|---|---|
| CysteineAlso: single arm interventional studyCysteine supplementation would be given according to the 2001 ROSS guidelines for the HCU. Cys amino acid supplements are available in the form of powder, each sachet containing 4gm which provides 500mg of Cys per sachet that is available in HMC medical store from where patients receive the medical formula and food at free of cost. The dosage of cysteine will be calculated according to the weight of the patient with the age specific recommendation and prescribed by the metabolic dietitian which will be approved by the metabolic physician prior to the supply of cysteine supplements to the patients. It is not known to have any serious adverse events that is life threatening. A single arm interventional study is opted as the intervention involves all the participants without withholding the treatment. Moreover, a single arm interventional study on cysteine supplementation aims to provide evidence on its efficacy contributing to the advancement of clinical practice in HCU management. | Dietary supplement | dietary management with additional Cysteine supplementation |
Primary outcome
improvement of the biochemical parameters specifically homocysteine and methionine levels
Time frame: Six months
Biochemical Parameters: Description: The primary outcome will assess the improvement in biochemical parameters, specifically homocysteine (umol/l) and methionine levels(umol/l), in patients with Homocystinuria (HCU) following Cysteine(Cys) supplementation. Measurement Tool: Blood tests will be used to measure the levels of homocysteine and methionine.
1 secondary outcome
Improvement of growth parameters including weight, Height and BMI
Time frame: six month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2024.
- Individual participant dataSharing planned: No. The country has strict laws preventing sharing of IPD to any third party.
Related trials for Classical Homocystinuria
RecruitingPhase 3
Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment
Homocystinuria
RecruitingPhase 1/2
Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)
Homocystinuria
Enrolling by invitationPhase 3
A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE)
Homocystinuria
RecruitingObservational study
Health Related Quality of Life (HrQoL) in Classical Homocystinuria (CBS Deficiency)
Homocystinuria
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cysteine in people with Classical Homocystinuria, run by Hamad Medical Corporation at 1 site in Qatar.
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 3 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 2 Oct 2024. 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 Qatar. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kala darling, Masters in Nutrition (800-555-5555, kdanial@hamad.qa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
improvement of the biochemical parameters specifically homocysteine and methionine levels (time frame: Six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Oct 2024.