Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP)

• ClinicalTrials.gov Identifier: NCT01617642
• Recruitment Status: Active, not recruiting
• First Posted: June 12, 2012
• Last Update Posted: January 23, 2023
• Sponsor: Nordlandssykehuset HF
• Collaborator: The Royal Norwegian Ministry of Health
• Information provided by (Responsible Party): Nordlandssykehuset HF

Study Description

Brief Summary:

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease, which is relatively prevalent in northern Norway with a total of around 90 patients. This provides us with a special opportunity to study AIP. AIP is caused by a mutation in the porphobilinogen deaminase, an enzyme in the haem synthesis. AIP presents symptoms, particularly among fertile women and older men. Typical symptoms are abdominal pain and dark red urine, nausea, vomiting, constipation, muscle weakness and nerve damage including paraesthesia and even paresis. This is known as symptomatic or manifest AIP (MAIP). Others do not display symptoms, so-called latent AIP (LAIP). AIP attacks may be triggered by a host of medicaments which affect the haem synthesis, infections, alcohol and stress. Treatments of manifestations include high sugar intake (4 sugar lumps/hour), alternatively administer glucose and Normosang (synthetic haem arginate) by intravenous injection and removing triggering factors. Diet, glucose intake, dental health and inflammatory parameters will be examined. This study can provide new knowledge about why only some people develop symptoms of AIP. Main hypothesis: There are differences in the diet, iron status, inflammation and glucose metabolism of the MAIP group vs. the LAIP group and the control group.

Condition or disease
Acute Intermittent Porphyria

Detailed Description:

In a group of people with proven acute intermittent porphyria (AIP) mutation, some will remain asymptomatic, while others have repeated periods of porphyria symptoms. Glucose inhibits ALA synthetase (ALAS), the first rate-limiting enzyme in the haem synthesis. Studies of individual patients point to the fact that increased glucose and/or fructose content in the diet inhibits porphyria attacks. A high sugar intake can reduce the disease activity in patients with AIP. The diet and related biomarkers of those with latent and manifest AIP will therefore be mapped to explain why some have latent and others have manifest acute intermittent porphyria. Other studies point to the fact that people with manifest AIP who have later developed diabetes type 2 no longer have porphyria symptoms. Dental health will also be examined.

Inflammation also affects the haem synthesis. Infections and/or inflammation are known to trigger AIP attacks. The disease activity in patients with acute intermittent porphyria in relation to inflammatory status, iron status, glucose metabolism and diet will therefore be examined.

The iron metabolism is interesting to study because it is believed that the overstimulation of the haem synthesis is what triggers porphyria attacks. Haem consists of iron and protoporphyrin IX, and it is therefore possible that iron supplements in cases of iron deficiency can induce increased haem synthesis and by doing so trigger and/or aggravate AIP.

Kidney failure is a serious secondary complication in some patients with MAIP. Protein markers for kidney injury in urine will be examined.

Study Design

• Study Type: Observational
• Actual Enrollment: 100 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP)
• Actual Study Start Date: July 1, 2012
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Groups and Cohorts

Group/Cohort
Control group; Healthy control group, matched for age and gender
Acute intermittent porphyria; Patients with acute intermittent porphyria.

Outcome Measures

Primary Outcome Measures :

1. Blood pressure [ Time Frame: Within 2 months after inclusion ]
   Resting systolic and diastolic blood pressure, a number of inflammatory parameters, serum markers for iron status and inflammation
2. Diet registration [ Time Frame: Within 2 months after inclusion ]
   Dietary registration during one week
3. Iron status [ Time Frame: Within 2 months after inclusion ]
   Blood samples for evaluation of iron status
4. Inflammatory status [ Time Frame: Within 2 months after inclusion ]
   Blood samples (cytokines etc) for evaluation of inflammation

Secondary Outcome Measures :

1. Dental health [ Time Frame: Within two months after inclusion ]
   Evaluate dental health through clinical examination

Biospecimen Retention:   Samples With DNA

Serum and plasma from 50 cases With acute intermittent porphyria and age, sex and place of 50 recidence matched controls. Urine samples. Pax tubes for RNA/DNA samples.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

The group of patients with acute intermittent porphyria will be recruited from primary care clinics and patient organizations.

The control group will be selected randomly from the same geographical area, matched for gender and age

Criteria

Inclusion Criteria:

• Diagnosed acute intermittent porphyria

Exclusion Criteria:

• Regulatory use of antiinflammatory drugs including steroids and NSAIDS
• Lacking consent competence

Contacts and Locations

Locations

Norway

Nordlandssykehuset HF

Bodø, Nordland, Norway, N-8092

Sponsors and Collaborators

Nordlandssykehuset HF

The Royal Norwegian Ministry of Health

Investigators

• Principal Investigator: Ole L Brekke, MD, PhD; University of Tromsø, Norway

More Information

Publications:

Storjord E, Dahl JA, Landsem A, Fure H, Ludviksen JK, Goldbeck-Wood S, Karlsen BO, Berg KS, Mollnes TE, W Nielsen E, Brekke OL. Systemic inflammation in acute intermittent porphyria: a case-control study. Clin Exp Immunol. 2017 Mar;187(3):466-479. doi: 10.1111/cei.12899. Epub 2016 Dec 15.

Storjord E, Dahl JA, Landsem A, Ludviksen JK, Karlsen MB, Karlsen BO, Brekke OL. Lifestyle factors including diet and biochemical biomarkers in acute intermittent porphyria: Results from a case-control study in northern Norway. Mol Genet Metab. 2019 Nov;128(3):254-270. doi: 10.1016/j.ymgme.2018.12.006. Epub 2018 Dec 10.

Henno LT, Storjord E, Christiansen D, Bergseth G, Ludviksen JK, Fure H, Barene S, Nielsen EW, Mollnes TE, Brekke OL. Effect of the anticoagulant, storage time and temperature of blood samples on the concentrations of 27 multiplex assayed cytokines - Consequences for defining reference values in healthy humans. Cytokine. 2017 Sep;97:86-95. doi: 10.1016/j.cyto.2017.05.014. Epub 2017 Jun 6.

Storjord E, Airila-Mansson S, Karlsen K, Madsen M, Dahl JA, Landsem A, Fure H, Ludviksen JK, Fjose JO, Dickey AK, Karlsen BO, Waage Nielsen E, Mollnes TE, Brekke OL. Dental and Periodontal Health in Acute Intermittent Porphyria. Life (Basel). 2022 Aug 19;12(8):1270. doi: 10.3390/life12081270.

• Responsible Party: Nordlandssykehuset HF
• ClinicalTrials.gov Identifier: NCT01617642
• Other Study ID Numbers: 2011/2197/REK; ID/7462 SFP 1068-12 ( Other Grant/Funding Number: Northern Norway Regional Health Authority )
• First Posted: June 12, 2012
• Last Update Posted: January 23, 2023
• Last Verified: January 2023

Keywords provided by Nordlandssykehuset HF:

Porphyria; Inflammation; Diet; Iron status

Additional relevant MeSH terms:

Porphyria, Acute Intermittent; Porphyria, Erythropoietic; Porphyrias; Inflammation; Pathologic Processes; Metabolic Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases