Observational Study of Acute Intermittent Porphyria Patients
Condition: Acute Intermittent Porphyria
MeSH terms: Porphyria, Acute Intermittent; Porphyria, Erythropoietic; Porphyrias
Study type: Observational

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 (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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Acute intermitent porphyria patients, with a severe condition. And genetic confirmation of
        Porphobilinogen deaminase mutation.
      
Biospecimen description: 
      Serum, urine
    
Keywords: Observational; Porphyria