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NCT Number: NCT06273644

Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment

The main aim of this clinical trial is to learn about the effect of carbohydrate-rich diet as a treatment for AIP (acute intermittent porphyria).

Aim: Investigate the diet's impact on tissue and serum glucose, plasma insulin, cytokine levels, amino acids, and gut microbiota in AIP, and their correlation with PBG (Porphobilinogen).

Aim: Assess the diet's effect on AIP symptoms and health status in AIP. Aim: Measure the effect of a high-carbohydrate diet on mitochondrial activity in AIP Aim: Map and detect potential mutations in mitochondrial genomic DNA in AIP Aim: Discover new markers in AIP through RNA sequencing and machine learning.

Participants will follow two diet plans, a 4-week intervention with 60-65 E% carbohydrates and a 4 week intervention with 40-45 E% carbohydrates.

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Key information

Conditions

Porphyria, Acute Intermittent Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Liver Diseases Metabolic Diseases Nutritional and Metabolic Diseases Porphyrias Porphyrias, Hepatic Skin Diseases Skin Diseases, Genetic Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Nordland Hospital Trust, Bodø, Nordland, Norway

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About this study

Acute intermittent porphyria (AIP) is an inherited disease that leads to the accumulation of porphobilinogen (PBG), resulting in severe abdominal pain, paralysis, fatigue, low-grade inflammation, and an increased risk of kidney failure and liver cancer. Studies at the cellular level and in mice have shown that elevated levels of glucose and insulin can affect heme synthesis, potentially reducing PBG levels. The investigators have previously demonstrated that individuals with AIP consume less carbohydrate (E% 40) than recommended. The investigators aim to conduct a crossover study involving 50 participants with AIP, where 50% will be subjected to a 4-week intervention with 60-65 E% carbohydrates, while the other half will consume 40-45 E% carbohydrates for 4 weeks. After a 4-week intervention-free period, the two groups will switch to the respective carbohydrate percentages. Symptoms, PBG levels, continuous tissue glucose, plasma/serum insulin, glucose, cytokines, amino acid levels, microbiota in the gut, body composition, and physical activity measured using accelerometers will be assessed before and after each intervention and compared. Mitochondrial activity will be assessed at the cellular level as oxidative activity. Mutations in mitochondrial DNA and RNA will also be examined since defects in oxidative energy metabolism are known to be associated with inflammation and cancer. The work will be carried out at Nordland Hospital and at the University of Oslo. The study will be coordinated and conducted by the Postdoc and partners at Nordland Hospital, Karolinska University Hospital Stockholm and Norrland University Hospital, Umeå, the University of Oslo, the Arctic University of Tromsø, and Nord University. Clinical nutritionists will create dietary plans, and bioengineers will perform analyses. Stay abroad for postdoc, and research cooperation, with porphyria researchers at UTMB, Texas and MGH, Boston, US.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of AIP

Exclusion criteria

  • Not having diagnosis of AIP
  • Undergoing treatment as part of other clinical research on AIP
  • Pregnancy
  • Diabetes
  • Below 18 years of age

Treatment and study plan

Carbohydrates

Other

Half of the patients will initially follow Diet Plan A with 60-65 E% carbohydrates for 4 weeks, followed by a 4-week washout period, and then Diet Plan B with 40-45 E% carbohydrates for 4 weeks. The other half will start with Diet Plan B for 4 weeks, followed by a 4-week washout period, and then Diet Plan A for 4 weeks . Diet Plans A and B contain recommended and adequate nutrients according to the Nordic Nutrition Recommendations 2023 (NNR2023) for maintaining a stable weight.

Primary outcomes

  1. Change in Urine Porphobilinogen/creatinine

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    AIP biochemical disease activity. First morning Urine Porphobilinogen/creatinine.

    Change from baseline before diet A to immediately after diet A, and change from baseline before diet B to immediately after diet B

  2. Urine Porphobilinogen/creatinine concentration, percentage change of repeated measurements

    Time frame: Day 1 ,4, 8, 11, 15, 18, 22, 25 and 29 of Diet Intervention A and of Diet Intervention B

    AIP biochemical disease activity, repeated measurements Percentage change in the median of repeated measurements of Urine Porphobilinogen/creatinine concentrations between Diet A and Diet B The repeated measurements in urine analyzed in urine samples from Day 1 ,4, 8, 11, 15, 18, 22, 25 and 29 of Diet A and of Diet B, and calculated median of Urine Porphobilinogen/creatinine concentration for diet A and median for diet B

Secondary outcomes

  1. Number of Hospitalizations,sick leaves, and doctor visits due to AIP

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Using questionnaire counting Number of hospitalizations, sick leaves, and doctor visits due to AIP

    • In the 4 weeks before Diet A, measured at baseline immediately before Diet A
    • In the 4 weeks of Diet A, measured immediately after Diet A.
    • In the 4 weeks before Diet B, measured at baseline immediately before Diet B
    • in the 4 weeks of Diet B, measured immediately after Diet B

  2. Health status

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    A standardized questionnaire assessing health (RAND-36) with a 4-week time frame from 0 (worst functioning) to 100 (best functioning), where 2 to 5 points represent a clinically meaningful difference based on data from other chronic diseases.

  3. Plasma Glucose level

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Plasma glucose concentration

  4. Interstitial fluid glucose level

    Time frame: Day 15 and 29 of diet A and day 15 and 29 of diet B

    Glucose measured in the interstitial fluid (ISF) Measuring is performed continuously by ISF glucose sensor FreeStyle Libre 3 in the 4 weeks of Diet A and in the 4 weeks of Diet B. Outcome is percentage change in the mean of repeated measurements between Diet A and Diet B.

    Each tissue glucose sensor lasts 14 days, and hence the outcome measure will be assessed each 14 days, and read in the LibreView program. The sensor is placed on the back of the participants upper arm

  5. Number of hypoglycemic events

    Time frame: Day 15 and 29 of diet A and day 15 and 29 of diet B

    Tissue glucose measured continuously by tissue glucose sensor FreeStyle Libre 3 (Abbott) in the 4 weeks during diet A and in the 4 weeks of diet B.

    Counting number of hypoglycemic events during the 4 weeks of diet A and comparing to counted number of hypoglycemic events during the 4 weeks of diet B.

    Each tissue glucose sensor lasts 14 days, and hence the outcome measure will be assessed each 14 days, and read in the LibreView program. Assessing is performed day 15 and day 29 of diet A and day 15 and 29 of diet B.

  6. Amino acid profile

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Levels of amino acids measured

  7. Plasma insulin, glucose, c-peptide

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Concentration levels measured in plasma

  8. HOMA score

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    HOMA score (Homeostatic Model Assessment) including estimated beta cell function, HOMA%B (%B), insulin sensitivity, HOMA%S (%S), and insulin resistance HOMA-IR (IR), calculated from insulin, glucose and C-peptide in plasma, using an Excel spreadsheet from the University of Oxford.

  9. HbA1c

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Concentration levels measured in blood

  10. Cytokines in plasma

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Cytokines, chemokines and growth factors measured using Multiplex assay from BioRad Lab, Bio-Plex 27-plex kit: Interleukin (IL)-1β, IL-1RA (IL-1 receptor antagonist), IL-2, IL-4, IL-5, IL-6, IL-7, chemokine (C-X-C) motif 8 (CXCL8), IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, chemokine (C-C motif) ligand 5 (CCL5), chemokine ligand 11 (CCL11), basic fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, CXCL10, CCL2, CCL3, CCL4, platelet-derived growth factor-BB (PDGF-BB), tumour necrosis factor (TNF) and vascular endothelial growth factor (VEGF).

  11. Intestinal microbiota composition

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Sequencing of fecal samples, Gut Health Panel from Bio-Me, covering 100 different bacterias

  12. Physical activity

    Time frame: Immediately after one week of Diet A, and immediately after one week of Diet B

    Accelerometer (AX3 Axivity Newcastle, UK), attached to the thigh and worn for 7 consecutive days in the first week of diet A and in the first week of diet B.

    Moderate to vigorous physical activity (MVPA) is detected in 5-second intervals. Measuring time (min/day) spent in MVPA during the first week of diet A and during the first week of diet B.

  13. Blood pressure

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    20 min measurement

  14. Body composition, metabolic age

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    Tanita Body Composition Analyzer

  15. Mitochondrial oxygen consumption rate

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    SeaHorse, mononuclear cells in peripheral blood

  16. ALAS1mRNA

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    TaqMan gene expression assay

  17. Urine-ALA/creatinine & urine-porphyrins

    Time frame: Baseline before diet A and immediately after the 4 weeks of diet A, baseline before diet B and immediately after the 4 weeks of diet B

    level measurement of concentration in urine

  18. Mitochondrial function-related genes

    Time frame: At baseline immediately before each participants first diet intervention

    Paxgen tubes, qPCR, Mitochondrial genome sequencing

Study contacts

Contact information is provided by the study sponsor or research team.

Elin Storjord, MD PhD

CONTACT

[email protected]

97072484

Hilde Thunhaug, Nurse

CONTACT

[email protected]

95057864

Sponsors and collaborators

Lead sponsor

Nordlandssykehuset HF

Other

Collaborators

  • Karolinska University Hospital
  • Nord University
  • Norwegian University of Science and Technology
  • The University of Texas Medical Branch, Galveston
  • UiT The Arctic University of Norway
  • University Hospital, Umeå
  • University of Oslo

Registry information

Important dates

Study start
2024
Primary completion
2027
Study completion
2037
First posted
Feb 22, 2024
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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