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Methylmalonic AcidemiaPROTECTNCT04176523

Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach

An observational study of Methylmalonic Acidemia and Propionic Acidemia, run by RECORDATI GROUP at 32 sites in 7 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a prospective mixed-design study focused on the long-term management of propionic aciduria (PA) and methylmalonic aciduria (MMA) with N-carbamylglutamate (NCG) maintenance therapy. Read more about this study

Who is it for?
Ages 6 months to 99 years
Conditions the study is for
Methylmalonic Acidemia, Propionic Acidemia
What is being tested?
Carglumic Acid
How many people
95 participants
Where
32 sitesin 7 countries
Study dates
15 Jan 2019to 30 Jul 2029
Phase
Observational
Are there results?
Not yet: the study is under way

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 6 months to 99 years
  • All sexes
  • Child, Adult, Older adult

Study population: Patients diagnosed with organic acideamia that have been on treatment with CARBAGLU® for a minimum of six months for the long-term management of their disease. This prospective observational study population will include up to 95 diagnosed MMA or PA patients with current carglumic acid treatment experience from 6 European countries: Sweden, the United Kingdom (UK), the Netherlands, Germany, Norway, Italy, Spain and France. The patients (or caregivers) included in this prospective observational study will also be invited to participate in a one-on-one phone interview.

Who may be able to join

  • Patient has confirmed diagnosis of an organic acidemia (e.g., MMA or PA)
  • Patient initiated treatment with carglumic acid for long-term management of MMA or PA
  • Patient has been treated with carglumic acid for a minimum of 6 months
  • Patient (or caregiver) is able to comply with all prospective study procedures
  • Patient (or caregiver) is able to provide informed consent

Who cannot join

  • None

Trial locations and contacts

32 sites in 7 countries. Contact the study team or a site near you to ask about taking part.

Vincenzo Giordano, MD contact

33 1 79911282

giordano.v@recordati.com

32 sites in 7 countries

Spain11 sites, 11 recruiting

  • AMM hospital val d'hebron

    Barcelona

    AMM hospital val d'hebron

    Recruiting

  • Sant Joan de Deu

    Barcelona

    Sant Joan de Deu

    Recruiting

  • Universitario de Cruces

    Bilbao

    Universitario de Cruces

    Recruiting

  • Hospital Infantil Universitario Nino Jesus

    Madrid, 28009

    Elvira Canedo-Villarroya, MD

    Consuelo Pedron-Giner, MD, 0034 915 03 59 33, consuelocarmen.pedron@salud.madrid.org

    Recruiting

  • Hospital 12 de Octubre

    Madrid, 28026

    Elena Martin-Hernandez, MD, 0034 913 90 88 86, emartinhernandez@salud.madrid.org

    Recruiting

  • Hospital Universitario La Paz

    Madrid, 28046

    Ana Morais-Lopez, MD, 0034 917 27 73 01, ana_morais_lopez@hotmail.com

    Recruiting

  • Universitario Ramon y Cajal Madrid

    Madrid

    Universitario Ramon Ramon y Cajal Madrid

    Recruiting

  • Hospital Universitario Virgen de la Arrixaca

    Murcia, 30120

    David Gil-Ortega, MD, 0034 609 08 23 44, d.gil.ortega@gmail.com

    Recruiting

  • Hospital Universitario Son Espases

    Palma de Mallorca, 07010

    Angeles Ruiz-Gomez, MD, 0034 659 71 96 81, ma.ruiz@ssib.es

    Recruiting

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

    Maria Bueno-Delgado, MD, 0034 616 11 98 97, mbuenod@yahoo.es

    Recruiting

  • Universitario Miguel Servet

    Zaragoza

    Universitario Miguel Servet

    Recruiting

Other trials in Spain

France8 sites, 8 recruiting

  • Hopital Des Enfants, CHU de Bordeaux-GH Pellegrin

    Bordeaux, 33076

    Delphine Lamireau, MD, 05.56.79.56.46, delphine.lamireau@chu-bordeaux.fr

    Recruiting

  • Hopital de la Conception

    Marseille, 13005

    Karin Mazodier, MD, 04.91.38.23.79, Karin.MAZODIER@ap-hm.fr

    Recruiting

  • Hôpital de la Timone

    Marseille, 13005

    Hôpital de la Timone

    Recruiting

  • CHU de Nancy - Hopitaux de Brabois

    Nancy, 54511

    Francois Feillet, MD, 03.83.15.47.96, f.feillet@chru-nancy.fr

    Recruiting

  • Hôpital Necker Enfants Malades

    Paris, 75015

    Hôpital Necker Enfants Malades

    Recruiting

  • CHU de Rouen

    Rouen, 76031

    Stephanie Torre, MD, 02.32.88.07.66, stephanie.torre@chu-rouen.fr

    Recruiting

  • Nouvel Hopital Civil

    Strasbourg, 67091

    Esther Noel, MD, 03.88.11.62.52, Esther.NOEL@chru-strasbourg.fr

    Recruiting

  • Hopital de Hautepierre

    Strasbourg, 67098

    Marie-Therese Abi-Warde, MD, 03.88.12.83.28, Marie-Therese.ABIWARDE@chru-strasbourg.fr

    Recruiting

Other trials in France

Italy7 sites, 7 recruiting

  • Azienda Ospedaliero Universitaria Meyer

    Florence, 50139

    Maria Alice Donati, MD

    Recruiting

  • San Paola Hospital, ASST Santi Paolo e Carlo

    Milan, 20142

    Sabrina Paci, MD

    Recruiting

  • Milan Policlinico University

    Milan

    Milan Policlinico University

    Recruiting

  • Azienda Ospedaliera San Gerardo Monza

    Monza, 20900

    Serena Gasperini, MD

    Recruiting

  • Azienda Ospedaliera Universitaria Federico II

    Naples, 80131

    Giancarlo Parenti, MD

    Recruiting

  • University Hospital of Padova

    Padova

    University Hospital of Padova

    Recruiting

  • Turin University Hospital

    Turin

    Turin University Hospital

    Recruiting

Other trials in Italy

United Kingdom3 sites, 3 recruiting

  • Guy's and St. Thomas' Hospital NHS Foundation Trust

    London, SE1 7EH

    Roshini Vara, MD, +44 ‭(0)20 7188 9412‬

    Recruiting

  • Great Ormond Street Hospital

    London, WC1N3JH

    James Davidson, MD, 44 207 4059200, james.davison@gosh.nhs.uk

    Recruiting

  • Sheffield Children's Hospital NHS Foundation Trust

    Sheffield, S10 2TH

    Sufin Yap, MD, sufin.yap@nhs.net

    Laura Looby, ‭‭‭+44 (0)115 ‭‭‭924 9924, laura.looby@nuh.nhs.uk

    Recruiting

Other trials in United Kingdom

Germany1 site, 1 recruiting

  • Klinikum Bremen Mitte, Prof. Hess Kinderklinik

    Bremen, 28205

    Alexandra Horbe-Blindt

    Recruiting

Other trials in Germany

Norway1 site, 1 recruiting

  • Oslo University Hospital

    Oslo, 0372

    Trine Tangeraas, MD, 0047 23 07 78 20, ttangera@ous-hf.no

    Recruiting

Other trials in Norway

Sweden1 site

  • NÄL

    Trollhättan

    Terminated

Other trials in Sweden

About this study

This is a prospective mixed-design study focused on the long-term management of propionic aciduria (PA) and methylmalonic aciduria (MMA) with N-carbamylglutamate (NCG) maintenance therapy. Treatment characteristics, clinical outcomes, and healthcare utilization data of patients diagnosed PA or MMA treated >6 months therapy with NCG are collected at baseline, 12 months, 18 months, 36 months and 54 months. Qualitative interviews with adult patients and caregivers are conducted >6 months after study enrollment to gain a better understanding of the disease burden and the treatment burden of patients and their families.

Read the detailed description

Study Design: This is a prospective, longitudinal, observational study of patients diagnosed with organic acidemia that has been on treatment with carglumic acid for a minimum of six months for the long-term management of their disease. This prospective observational study population will include up to 85 diagnosed MMA or PA patients with current carglumic acid treatment experience from 6 European countries: Sweden, the United Kingdom (UK), the Netherlands, Germany, Norway, Italy, Spain and France. The patients (or caregivers) included in this prospective observational study will also be invited to participate in a one-on-one phone interview.

Study Procedures: After Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approval is obtained for the protocol and all supporting protocol documents, clinicians caring for patients with MMA or PA will provide their patients (or caregivers) with the opportunity to participate in the study. Patients (or caregivers) will receive an Information Letter (PIL) (Appendices A and B) inviting them (or their caregiver) to take part in a prospective observational study and in a one-on-one phone interview.

Patients (or caregivers) who are interested in participating in this observational/interview study will review the informed consent form (Appendices C and D) with the clinician and his/her research team. If agreeable, patients (or caregivers) will be asked to sign the consent form and a countersigned copy will be provided to them for their records. Clinicians and their research team at each site will then review patient charts and record demographic and medical history information for each patient. Patient information from medical charts will be collected at the start of the study (baseline), and 12 months and 18 months, and 36 months, and 54 months after baseline. All information derived from medical chart reviews will be recorded through web-based Electronic Data Capture system (EDC).

Patients (or caregivers) who agree to participate in a one-on-one phone interview will provide contact information for their clinicians and the respective research team to include in the Contact Information Form (CIF) (Appendix E). Researchers will then contact patients (or caregivers) directly to schedule a one-hour phone interview. An interview guide (Appendices F and G) including open-ended questions and probes will be used to elicit concepts and orient the discussion during the interview. Patient (or caregiver) interviews will focus on describing the symptoms and impacts of MMA or PA, as well as patient treatment experiences with carglumic acid, their treatment preferences, and their satisfaction with treatment. At the end of the interview, patients (or caregivers) will be asked to complete a Demographic and Health Information Form (DHIF; Appendices H and I). Phone interviews will be audio-recorded with the patient's (or caregiver) permission, transcribed and translated (as needed) in preparation for qualitative analysis.

Data Analysis: The primary prospective data analysis will involve a comparison of the incidence and duration of decompensation episodes pre- and post- initiation of carglumic acid. Additional analysis will include healthcare resource utilization around individual decompensation events, patient/caregiver burden, and patient/caregiver satisfaction with treatment. All prospective data will be undertaken using SAS® software, version 9.4 of the SAS® system for Windows (Cary, NC, USA). All qualitative data from the interviews will be analyzed using ATLAS.ti, a software package uniquely designed to analyze qualitative data. The audio-recorded verbatim transcripts of the interviews will be coded to identify patterns in participants' responses concerning patient experiences with the symptoms and impacts of MMA or PA, treatment experience with carglumic acid, patient treatment preferences, and treatment satisfaction. Findings will be summarized in a final report and may be published or presented by the investigator(s) after the review by, and in consultation and agreement with, the sponsor. If published or presented, the results will be presented in such a way that confidential or proprietary information is not disclosed.

Being tested
Carglumic Acid
Medical subject headings
Methylmalonic acidemia, Propionic Acidemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carglumic AcidDrug

    Also called Carbaglu

    Maintenance therapy with carglumic acid

Study groups in NCT04176523
Study groupRoleWhat they receive
Methylmalonic_acidemiaPatients with confirmed diagnosis of methylmalonic acidemia, and treated with carglumic acid, at any dose form, any dosage,
Receives: Drug: Carglumic Acid
Propionic_AcidemiaPatients with confirmed diagnosis of propionic acidemia, and treated with carglumic acid, at any dose
Receives: Drug: Carglumic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Number and Duration of Decompensation Events

    Change in the number of decompensation events before and after treatment with carglumic acid

    Measured: 54 months

Secondary outcomes (4)

  1. Frequency and Duration of Healthcare Resource Utilization

    Estimation of the health care resource utilization associated with a decompensation event with number of inpatient hospitalization vs. outpatient vs. home. Treatment used to control ammonia levels during decompensation episodes. Number of emergency visits. number of visits to specialist or to general practitioner. Number of hospital stays. Number of bed days in hospital.

    Measured: 18 months

  2. Caregiver Burden Exposure Frequency and Duration

    description of the patient and caregiver burden associated with MMA and PA

    Measured: 18 months

  3. Caregiver Satisfaction Level

    Describe the MMA and PA patient and caregiver satisfaction with MMA or PA treatment

    Measured: 18 months

  4. Maintenance Dosage of NCG

    Document the dosages of NCG used in maintenance treatment

    Measured: 54 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2019
  2. Study start15 Jan 2019
  3. Primary completion30 Dec 2024 (estimated)
  4. Study completion30 Jul 2029 (estimated)

Resources

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
Case only
Time perspective
Prospective
Enrolment
95 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04176523
Sponsor's protocol ID
17180
Acronym
PROTECT
Status last verified
Feb 2024
First submitted
20 Nov 2019
Last updated
5 Feb 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Burlina A, Bettocchi I, Biasucci G, Bordugo A, Gasperini S, La Spina L, Maines E, Meli C, Menni F, Paci S, Procopio E, Rossi A, Rubert L, Spada M, Tubili F, Tummolo A. Long-term use of carglumic acid in methylmalonic aciduria, propionic aciduria and isovaleric aciduria in Italy: a qualitative survey. Eur Rev Med Pharmacol Sci. 2022 Jul;26(14):5136-5143. doi: 10.26355/eurrev_202207_29302.

    PubMed 35916811

  • Alfadhel M, Nashabat M, Saleh M, Elamin M, Alfares A, Al Othaim A, Umair M, Ahmed H, Ababneh F, Al Mutairi F, Eyaid W, Alswaid A, Alohali L, Faqeih E, Almannai M, Aljeraisy M, Albdah B, Hussein MA, Rahbeeni Z, Alasmari A. Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial. Orphanet J Rare Dis. 2021 Oct 11;16(1):422. doi: 10.1186/s13023-021-02032-8.

    PubMed 34635114

  • Kido J, Matsumoto S, Nakamura K. Carglumic Acid Contributes to a Favorable Clinical Course in a Case of Severe Propionic Acidemia. Case Rep Pediatr. 2020 Mar 9;2020:4709548. doi: 10.1155/2020/4709548. eCollection 2020.

    PubMed 32231837

  • Kiykim E, Oguz O, Duman C, Zubarioglu T, Cansever MS, Zeybek ACA. Long-term N-carbamylglutamate treatment of hyperammonemia in patients with classic organic acidemias. Mol Genet Metab Rep. 2021 Jan 30;26:100715. doi: 10.1016/j.ymgmr.2021.100715. eCollection 2021 Mar.

    PubMed 33552909

  • Tummolo A, Melpignano L, Carella A, Di Mauro AM, Piccinno E, Vendemiale M, Ortolani F, Fedele S, Masciopinto M, Papadia F. Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report. J Med Case Rep. 2018 Apr 22;12(1):103. doi: 10.1186/s13256-018-1631-1.

    PubMed 29679984

  • Burlina A, Cazzorla C, Zanonato E, Viggiano E, Fasan I, Polo G. Clinical experience with N-carbamylglutamate in a single-centre cohort of patients with propionic and methylmalonic aciduria. Mol Genet Metab Rep. 2016 Jul 13;8:34-40. doi: 10.1016/j.ymgmr.2016.06.007. eCollection 2016 Sep.

    PubMed 27489777

  • Yap S, Lamireau D, Feillet F, Ruiz Gomez A, Davison J, Tangeraas T, Giordano V. Real-World Experience of Carglumic Acid for Methylmalonic and Propionic Acidurias: An Interim Analysis of the Multicentre Observational PROTECT Study. Drugs R D. 2024 Mar;24(1):69-80. doi: 10.1007/s40268-023-00449-z. Epub 2024 Jan 10.

    PubMed 38198106

  • Yap S, Procopio E, Rossi A, Burlina A, Dougherty-de Miguel L, Canedo E, Furlan F, Stanescu S, Delcroix T, Boutoub Z, Giordano V. Real world experience of carglumic acid for methylmalonic and propionic acidurias: the second interim analysis of the multicentre observational PROTECT study. Orphanet J Rare Dis. 2026 Aug 3;21(1):348. doi: 10.1186/s13023-026-04522-z.

    PubMed 42839282

Questions about this trial

What is this clinical trial studying?

An observational study of Methylmalonic Acidemia and Propionic Acidemia, run by RECORDATI GROUP at 32 sites in 7 countries.

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 5 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 5 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in Spain, France, Italy, United Kingdom, Germany and 2 more countries. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Vincenzo Giordano, MD (33 1 79911282, giordano.v@recordati.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Number and Duration of Decompensation Events (time frame: 54 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 NCT04176523, which also lists 8 linked publications.

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 5 Feb 2024.

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