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

Acute Intermittent Porphyria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01617642
• Other study ID #: 2011/2197/REK
• Secondary ID: ID/7462 SFP 1068
• Status: Active, not recruiting
• Start date: July 1, 2012
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Nordlandssykehuset HF
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed acute intermittent porphyria

Exclusion Criteria:

• Regulatory use of antiinflammatory drugs including steroids and NSAIDS

• Lacking consent competence

Related Conditions & MeSH terms

• Acute Intermittent Porphyria
• Inflammation
• Porphyria, Acute Intermittent
• Porphyria, Erythropoietic
• Porphyrias

Locations

Country	Name	City	State
Norway	Nordlandssykehuset HF	Bodø	Nordland

Sponsors (2)

Lead Sponsor	Collaborator
Nordlandssykehuset HF	The Royal Norwegian Ministry of Health

Country where clinical trial is conducted

Norway, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Storjord E, Wahlin S, Karlsen BO, Hardersen RI, Dickey AK, Ludviksen JK, Brekke OL. Potential Biomarkers for the Earlier Diagnosis of Kidney and Liver Damage in Acute Intermittent Porphyria. Life (Basel). 2023 Dec 21;14(1):19. doi: 10.3390/life14010019. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood pressure	Resting systolic and diastolic blood pressure, a number of inflammatory parameters, serum markers for iron status and inflammation	Within 2 months after inclusion
Primary	Diet registration	Dietary registration during one week	Within 2 months after inclusion
Primary	Iron status	Blood samples for evaluation of iron status	Within 2 months after inclusion
Primary	Inflammatory status	Blood samples (cytokines etc) for evaluation of inflammation	Within 2 months after inclusion
Secondary	Dental health	Evaluate dental health through clinical examination	Within two months after inclusion