Observational Study of Acute Intermittent Porphyria Patients
Keywords
Abstract
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.
Dates
| Last Verified: | 01/31/2014 |
| First Submitted: | 02/26/2014 |
| Estimated Enrollment Submitted: | 03/02/2014 |
| First Posted: | 03/03/2014 |
| Last Update Submitted: | 03/10/2014 |
| Last Update Posted: | 03/11/2014 |
| Actual Study Start Date: | 07/31/2011 |
| Estimated Primary Completion Date: | 06/30/2013 |
| Estimated Study Completion Date: | 01/31/2014 |
Condition or disease
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| 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). |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Sampling method | Non-Probability Sample |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - 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. Exclusion Criteria: - 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. |
Outcome
Primary Outcome Measures
1. Changes of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) urinary levels in AIP patients [up to 24 months]
Secondary Outcome Measures
1. Clinical Evolution of acute intermittent porphyria. Frecuency of hospitalizations [up to 24 months]
2. Psychological evaluation of patients [up to 24 months]
3. Health related quality of life [up to 24 months]
4. Frequency of AIP symptoms [up to 24 months]
5. Frequency of treatments for AIP symptoms [up to 24 months]
Other Outcome Measures
1. Immunogenicity analysis [up to 24 months]
2. Biological markers identification [up to 24 months]
