Acute Intermittent PorphyriaNCT02076763
Observational Study of Acute Intermittent Porphyria Patients
An observational study of Acute Intermittent Porphyria, run by Digna Biotech S.L. at 2 sites in Spain.
Trial summary
This is an observational prospective study that will allow evaluating the clinical and laboratory parameters evolution of at least eight patients with AIP. This study will allow establishing a baseline for the evaluation of the eight patients that are planned to be included in a gene therapy clinical trial… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Intermittent Porphyria
- How many people
- 9 participants
- Where
- 2 sitesSpain
- Study dates
- Aug 2011to Feb 2014
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Acute intermitent porphyria patients, with a severe condition. And genetic confirmation of Porphobilinogen deaminase mutation.
Who may be able to join
- Patient's written consent to take part in the study after receiving all the information regarding the design, objectives and potential risks that may arise during the observational study; as well as general information about the subsequent clinical trial.
- Age between 18 and 65 years, inclusively.
- Patient diagnosed of AIP (by clinical, biochemical data and genetic confirmation of porphobilinogen deaminase (PBGD) gene mutation). The patient must have a severe AIP condition, with at least two hospitalizations during the previous year due to acute attacks (clinical manifestations of acute porphyria), or at least four hospitalizations during the previous year due to the requirement of hospital treatment administration (including day-hospital and home hospital program).
- Ability to follow instructions and cooperate during the study conduct.
Who cannot join
- Pregnant women, positive urine pregnancy test, or intention of becoming pregnant.
- Acute or chronic liver disease for viral, autoimmune or metabolic cause, gastrointestinal dysfunction (different from those typical gastrointestinal symptoms of an acute attack of AIP), kidney disorder (renal impairment defined as plasma creatinine > 2 mg/dl (150 µmol/l)), severe respiratory disease, severe autoimmune disease or severe acute active infectious condition.
- Presence of adeno-associated virus type 5 (AAV5) neutralizing antibodies.
- Positive hepatitis B or C virus (HBV or HCV) serological test.
- Positive human immunodeficiency virus (HIV) serological test.
- History of drug (cannabis, cocaine, amphetamines, barbiturates) or alcohol abuse or addiction, during the three months preceding the initial visit.
- Current or previous participation in a gene therapy trial.
- Any other disease or condition that, in the opinion of the principal investigator, contraindicates their participation in the study because it can expose the patient to a risk or because disqualifies the patient to complete the timetable of the study.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
12 Octubre Hospital
Madrid, Madrid, 28041
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
About this study
This is an observational prospective study that will allow evaluating the clinical and laboratory parameters evolution of at least eight patients with AIP.
This study will allow establishing a baseline for the evaluation of the eight patients that are planned to be included in a gene therapy clinical trial (AAVPBGD-AIP-001) for the AIP treatment using a rAAV5-AAT-cohPBGD expression.
Read more
Patients fulfilling the study inclusion criteria will undergo a clinical and laboratory evaluation for a minimum of 6 months (with one inclusion visit, one final visit and at least two visits of follow up) up to a maximum of 24 months until their inclusion in the subsequent clinical trial.
A complete evaluation of the clinical (symptoms and quality of life assessment) and laboratory (blood and urine) data will be collected.
Read the detailed description
Acute Intermittent Porphyria (AIP) is inherited as an autosomal dominant disorder of the heme biosynthesis pathway. AIP is caused by a genetic defect in porphobilinogen deaminase (PBGD) a key enzyme for heme synthesis.
AIP is characterized by acute episodes and asymptomatic periods. Neuropathic symptoms are predominantly in these attacks, which may be related to the toxic effect produced by the precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), accumulated because the enzyme deficiency. It occurs with very low prevalence (1 in 50,000), but figures for prevalence based on clinical manifestations (i.e., acute attacks) greatly underestimate the number of patients with latent AIP.
Abdominal pain is the most common symptom, sometimes with constipation. Paraesthesias and paralysis also occur, and death may result from respiratory paralysis. Many other phenomena, including seizures, psychotic episodes, and hypertension, develop during acute attacks (Kadish 1999, Anderson 2007). Acute attacks rarely occur before puberty. They may be precipitated by porphyrogenic drugs such as barbiturates, progestogens and sulfonamides, some of which are known to induce the first rate-controlling step in heme synthesis, ALA synthesis. Other known precipitants are alcohol, infection, starvation, and hormonal changes; attacks are more common in women.
This is a pre-treatment observational study designed to collect clinical and laboratory data to later compare baseline and post-treatment variables in a future clinical trial (AAVPBGD-AIP-001) for the AIP treatment using a recombinant adeno-associated virus vector with a liver-specific promoter for the PBGD expression (rAAV5-AAT-cohPBGD).
The PRIMARY OBJECTIVE is to observe the changes of PBG and ALA urinary levels in AIP patients.
The SECONDARY OBJECTIVES are:
- To observe and document the frequency of acute attacks, the nature and frequency of symptoms, medication and hospitalization requirements, neurological involvement, psychological involvement and health-related quality of life of AIP patients.
- To record the use of concomitant medication in AIP patients.
At least eight patients fulfilling the inclusion/exclusion criteria will be included. No sample size assessments have been taken into account due to the study nature, so this number of patients is considered sufficient to meet the study objectives.
- Conditions
- Acute Intermittent Porphyria
- Keywords
- Observational, Porphyria
- Medical subject headings
- Porphyria, Acute Intermittent, Porphyrias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Acute intermittent porphyria | Patient diagnosed of AIP (by clinical, biochemical data and genetic confirmation of porphobilinogen deaminase (PBGD) gene mutation). The patient must have a severe AIP condition, with at least two hospitalizations during the previous year due to acute attacks (clinical manifestations of acute porphyria), or at least four hospitalizations during the previous year due to the requirement of hospital treatment administration (including day-hospital and home hospital program). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) urinary levels in AIP patients
The primary objective of this study is to observe the changes of PBG and ALA urinary levels in acute intermittent porphyria patients. The patient will collect an early morning single urine sample protected from light, for the determination of PBG and ALA during each of the study visits (inclusion, follow-up and final visits). If hemin or glucose treatments were necessary, the patient should collect a urine sample before treatment administration, and sent it or carry it to the local investigation center.
Measured: up to 24 months
Secondary outcomes (5)
Clinical Evolution of acute intermittent porphyria. Frecuency of hospitalizations
The information regarding the need and frequency of hospitalizations will be collected.
Measured: up to 24 months
Psychological evaluation of patients
The presence and level of anxiety and depression will be assessed by using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) rating scales.
Measured: up to 24 months
Health related quality of life
Health-related quality of life will be assessed through the SF-36v2 questionnaire.
Measured: up to 24 months
Frequency of AIP symptoms
The frequency of gastrointestinal, neurological, cardiovascular symptoms, abdominal pain and osteo-muscular pain, any other symptoms that may be considered associated with AIP will be collected.
Measured: up to 24 months
Frequency of treatments for AIP symptoms
The information regarding the need and frequency of specific treatments for symptoms control (analgesics, hemin and glucose endovenous solution), will be collected.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study startAug 2011
- Primary completionJul 2013
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Intermittent PorphyriaStudies 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
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Digna Biotech S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Porphyria Centre Sweden, University of Navarra, UniQure N.V.
- Responsible party
- Sponsor
- Investigators
- Juan Ruiz, MD, Study chair, Digna Biotech S.L.Jesus Prieto, MD, Principal investigator, Clinica Universidad de NavarraRafael Enriquez de Salamanca, MD, Principal investigator, Hospital 12 Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02076763
- Sponsor's protocol ID
- DIG-API-2011-01
- Other IDs
- 261506 AIPGene
- Status last verified
- Feb 2014
- First submitted
- 27 Feb 2014
- Last updated
- 12 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Jerico D, Luis EO, Cusso L, Fernandez-Seara MA, Morales X, Cordoba KM, Benito M, Sampedro A, Larriva M, Ramirez MJ, de Salamanca RE, Ortiz-de-Solorzano C, Alegre M, Prieto J, Lanciego JL, D'Avola D, Gonzalez-Aseguinolaza G, Pastor MA, Desco M, Fontanellas A. Brain ventricular enlargement in human and murine acute intermittent porphyria. Hum Mol Genet. 2020 Nov 25;29(19):3211-3223. doi: 10.1093/hmg/ddaa204.
PubMed 32916704D'Avola D, Lopez-Franco E, Sangro B, Paneda A, Grossios N, Gil-Farina I, Benito A, Twisk J, Paz M, Ruiz J, Schmidt M, Petry H, Harper P, de Salamanca RE, Fontanellas A, Prieto J, Gonzalez-Aseguinolaza G. Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria. J Hepatol. 2016 Oct;65(4):776-783. doi: 10.1016/j.jhep.2016.05.012. Epub 2016 May 17.
PubMed 27212246
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study of Acute Intermittent Porphyria Patients
- ClinicalTrials.gov ID
- NCT02076763
- Acronym / sponsor ID
- DIG-API-2011-01
- Conditions
- Acute Intermittent Porphyria
- Keywords
- Observational, Porphyria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Digna Biotech S.L.Industry (pharma, biotech, devices)
- Collaborators
- Porphyria Centre Sweden, University of Navarra, UniQure N.V.
- Study start
- Aug 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 4 Mar 2014 (estimated)
- 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.
This is an observational prospective study that will allow evaluating the clinical and laboratory parameters evolution of at least eight patients with AIP.
This study will allow establishing a baseline for the evaluation of the eight patients that are planned to be included in a gene therapy clinical trial (AAVPBGD-AIP-001) for the AIP treatment using a rAAV5-AAT-cohPBGD expression.
Patients fulfilling the study inclusion criteria will undergo a clinical and laboratory evaluation for a minimum of 6 months (with one inclusion visit, one final visit and at least two visits of follow up) up to a maximum of 24 months until their inclusion in the subsequent clinical trial.
A complete evaluation of the clinical (symptoms and quality of life assessment) and laboratory (blood and urine) data will be collected.
Detailed description
Acute Intermittent Porphyria (AIP) is inherited as an autosomal dominant disorder of the heme biosynthesis pathway. AIP is caused by a genetic defect in porphobilinogen deaminase (PBGD) a key enzyme for heme synthesis.
AIP is characterized by acute episodes and asymptomatic periods. Neuropathic symptoms are predominantly in these attacks, which may be related to the toxic effect produced by the precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), accumulated because the enzyme deficiency. It occurs with very low prevalence (1 in 50,000), but figures for prevalence based on clinical manifestations (i.e., acute attacks) greatly underestimate the number of patients with latent AIP.
Abdominal pain is the most common symptom, sometimes with constipation. Paraesthesias and paralysis also occur, and death may result from respiratory paralysis. Many other phenomena, including seizures, psychotic episodes, and hypertension, develop during acute attacks (Kadish 1999, Anderson 2007). Acute attacks rarely occur before puberty. They may be precipitated by porphyrogenic drugs such as barbiturates, progestogens and sulfonamides, some of which are known to induce the first rate-controlling step in heme synthesis, ALA synthesis. Other known precipitants are alcohol, infection, starvation, and hormonal changes; attacks are more common in women.
This is a pre-treatment observational study designed to collect clinical and laboratory data to later compare baseline and post-treatment variables in a future clinical trial (AAVPBGD-AIP-001) for the AIP treatment using a recombinant adeno-associated virus vector with a liver-specific promoter for the PBGD expression (rAAV5-AAT-cohPBGD).
The PRIMARY OBJECTIVE is to observe the changes of PBG and ALA urinary levels in AIP patients.
The SECONDARY OBJECTIVES are:
- To observe and document the frequency of acute attacks, the nature and frequency of symptoms, medication and hospitalization requirements, neurological involvement, psychological involvement and health-related quality of life of AIP patients.
- To record the use of concomitant medication in AIP patients.
At least eight patients fulfilling the inclusion/exclusion criteria will be included. No sample size assessments have been taken into account due to the study nature, so this number of patients is considered sufficient to meet the study objectives.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute intermittent porphyria | – | –Patient diagnosed of AIP (by clinical, biochemical data and genetic confirmation of porphobilinogen deaminase (PBGD) gene mutation). The patient must have a severe AIP condition, with at least two hospitalizations during the previous year due to acute attacks (clinical manifestations of acute porphyria), or at least four hospitalizations during the previous year due to the requirement of hospital treatment administration (including day-hospital and home hospital program). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Acute intermitent porphyria patients, with a severe condition. And genetic confirmation of Porphobilinogen deaminase mutation.
Key inclusion criteria (4 listed)
- Patient's written consent to take part in the study after receiving all the information regarding the design, objectives and potential risks that may arise during the observational study; as well as general information about the subsequent clinical trial.
- Age between 18 and 65 years, inclusively.
- Patient diagnosed of AIP (by clinical, biochemical data and genetic confirmation of porphobilinogen deaminase (PBGD) gene mutation). The patient must have a severe AIP condition, with at least two hospitalizations during the previous year due to acute attacks (clinical manifestations of acute porphyria), or at least four hospitalizations during the previous year due to the requirement of hospital treatment administration (including day-hospital and home hospital program).
- Ability to follow instructions and cooperate during the study conduct.
Key exclusion criteria (8 listed)
- Pregnant women, positive urine pregnancy test, or intention of becoming pregnant.
- Acute or chronic liver disease for viral, autoimmune or metabolic cause, gastrointestinal dysfunction (different from those typical gastrointestinal symptoms of an acute attack of AIP), kidney disorder (renal impairment defined as plasma creatinine > 2 mg/dl (150 µmol/l)), severe respiratory disease, severe autoimmune disease or severe acute active infectious condition.
- Presence of adeno-associated virus type 5 (AAV5) neutralizing antibodies.
- Positive hepatitis B or C virus (HBV or HCV) serological test.
- Positive human immunodeficiency virus (HIV) serological test.
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
Changes of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) urinary levels in AIP patients
Time frame: up to 24 months
The primary objective of this study is to observe the changes of PBG and ALA urinary levels in acute intermittent porphyria patients. The patient will collect an early morning single urine sample protected from light, for the determination of PBG and ALA during each of the study visits (inclusion, follow-up and final visits). If hemin or glucose treatments were necessary, the patient should collect a urine sample before treatment administration, and sent it or carry it to the local investigation center.
5 secondary outcomes
Clinical Evolution of acute intermittent porphyria. Frecuency of hospitalizations
Time frame: up to 24 months
Psychological evaluation of patients
Time frame: up to 24 months
Health related quality of life
Time frame: up to 24 months
Frequency of AIP symptoms
Time frame: up to 24 months
Frequency of treatments for AIP symptoms
Time frame: up to 24 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 12 Mar 2014.
- Derived from this study: PubMed 32916704Jerico D, Luis EO, Cusso L, Fernandez-Seara MA, Morales X, Cordoba KM, Benito M, Sampedro A, Larriva M, Ramirez MJ, de Salamanca RE, Ortiz-de-Solorzano C, Alegre M, Prieto J, Lanciego JL, D'Avola D, Gonzalez-Aseguinolaza G, Pastor MA, Desco M, Fontanellas A. Brain ventricular enlargement in human and murine acute intermittent porphyria. Hum Mol Genet. 2020 Nov 25;29(19):3211-3223. doi: 10.1093/hmg/ddaa204.
- Derived from this study: PubMed 27212246D'Avola D, Lopez-Franco E, Sangro B, Paneda A, Grossios N, Gil-Farina I, Benito A, Twisk J, Paz M, Ruiz J, Schmidt M, Petry H, Harper P, de Salamanca RE, Fontanellas A, Prieto J, Gonzalez-Aseguinolaza G. Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria. J Hepatol. 2016 Oct;65(4):776-783. doi: 10.1016/j.jhep.2016.05.012. Epub 2016 May 17.
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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.
Juan Ruiz, MD study chair
Digna Biotech S.L.
Jesus Prieto, MD principal investigator
Clinica Universidad de Navarra
Rafael Enriquez de Salamanca, MD principal investigator
Hospital 12 Octubre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Intermittent Porphyria, run by Digna Biotech S.L. at 2 sites in Spain.
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 4 inclusion and 8 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: finished, as of the sponsor's last update on 12 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. 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?
Changes of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) urinary levels in AIP patients (time frame: up to 24 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 NCT02076763, which also lists 2 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 12 Mar 2014.