Clinical Trial: Observational Study of Acute Intermittent Porphyria Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Observational Study of Acute Intermittent Porphyria Patients

Brief 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 Summary:

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
Sponsor: Digna Biotech S.L.

Current 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Clinical Evolution of acute intermittent porphyria. Frecuency of hospitalizations [ Time Frame: up to 24 months ]
    The information regarding the need and frequency of hospitalizations will be collected.
  • Psychological evaluation of patients [ Time Frame: up to 24 months ]
    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.
  • Health related quality of life [ Time Frame: up to 24 months ]
    Health-related quality of life will be assessed through the SF-36v2 questionnaire.
  • Frequency of AIP symptoms [ Time Frame: up to 24 months ]
    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.
  • Frequency of treatments for AIP symptoms [ Time Frame: up to 24 months ]
    The information regarding the need and frequency of specific treatments for symptoms control (analgesics, hemin and glucose endovenous solution), will be collected.


Original Secondary Outcome: Same as current

Information By: Digna Biotech S.L.

Dates:
Date Received: February 27, 2014
Date Started: August 2011
Date Completion:
Last Updated: March 11, 2014
Last Verified: February 2014