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| Name | Class |
|---|---|
| University of Oslo | OTHER |
| Nord University | OTHER |
| UiT The Arctic University of Norway | OTHER |
| Norwegian University of Science and Technology |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 60-65 E% Carbohydrates | Experimental | Diet plan A with 60-65 E% Carbohydrates in 4 weeks |
|
| 40-45% Carbohydrates | Active Comparator | Diet plan B with 40-45 E% Carbohydrates in 4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Urine Porphobilinogen/creatinine | 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 | 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 |
| Urine Porphobilinogen/creatinine concentration, percentage change of repeated measurements | 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 | Day 1 ,4, 8, 11, 15, 18, 22, 25 and 29 of Diet Intervention A and of Diet Intervention B |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Hospitalizations,sick leaves, and doctor visits due to AIP | Using questionnaire counting Number of hospitalizations, sick leaves, and doctor visits due to AIP
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Elin Storjord, MD PhD | Contact | 97072484 | elin.storjord@nordlandssykehuset.no | |
| Hilde Thunhaug, Nurse | Contact | 95057864 | hilde.thunhaug@nordlandssykehuset.no |
| Name | Affiliation | Role |
|---|---|---|
| Elin Storjord, MD PhD | Nordlandssykehuset HF | Principal Investigator |
| Per Dahlqvist, MD PhD | Norrland University Hospital, Umeå | Principal Investigator |
| Eliane Sardh, MD PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nordland Hospital Trust | Recruiting | Bodø | Nordland | 8092 | Norway |
Selected Individual participant data that underlie the results reported in published articles, can be accessed upon reasonable request to the principal investigator, but in each case the data will be deidentified, and the data can only be shared if it is considered that it will not be possible to reidentify persons from the data, and if in each case the data protection officer has advised it and the principal investigator has granted it.
Due to Norwegian law on sensitive data, raw data of this type cannot be submitted to public repositories, e.g DNA sequencing data.
Study protocol and the template for informed consent form is available upon reasonable request.
Immediately following each publication. Until 31 of December 2037
Reasonable request
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| ID | Term |
|---|---|
| D017118 | Porphyria, Acute Intermittent |
| ID | Term |
|---|---|
| D017094 | Porphyrias, Hepatic |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D012873 | Skin Diseases, Genetic |
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| ID | Term |
|---|---|
| D002241 | Carbohydrates |
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| OTHER |
| The University of Texas Medical Branch, Galveston | OTHER |
| Karolinska University Hospital | OTHER |
| University Hospital, Umeå | OTHER |
The study is a crossover study involving 50 individuals with AIP. The study design was chosen to determine whether the treatment has an effect compared to baseline analyses and whether the sequence of treatment has an effect, as well as whether one of the interventions is more effective than the other.
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Blinding is attempted by labeling the provided diet plans as A and B. The physician recording outcome variables and the researcher performing statistical analysis are blinded to the given diet.
|
| 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 |
| Health status | 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. | 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 level | Plasma glucose concentration | 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 |
| Interstitial fluid glucose level | 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 | Day 15 and 29 of diet A and day 15 and 29 of diet B |
| Number of hypoglycemic events | 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. | Day 15 and 29 of diet A and day 15 and 29 of diet B |
| Amino acid profile | Levels of amino acids measured | 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 insulin, glucose, c-peptide | Concentration levels measured in plasma | 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 | 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. | 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 |
| HbA1c | Concentration levels measured in blood | 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 in plasma | 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). | 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 |
| Intestinal microbiota composition | Sequencing of fecal samples, Gut Health Panel from Bio-Me, covering 100 different bacterias | 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 |
| Physical activity | 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. | Immediately after one week of Diet A, and immediately after one week of Diet B |
| Blood pressure | 20 min measurement | 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 |
| Body composition, metabolic age | Tanita Body Composition Analyzer | 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 |
| Mitochondrial oxygen consumption rate | SeaHorse, mononuclear cells in peripheral blood | 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 |
| ALAS1mRNA | TaqMan gene expression assay | 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 |
| Urine-ALA/creatinine & urine-porphyrins | level measurement of concentration in urine | 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 |
| Mitochondrial function-related genes | Paxgen tubes, qPCR, Mitochondrial genome sequencing | At baseline immediately before each participants first diet intervention |
| Studieenheten, Akademiskt Specialistcentrum, Stockholm Läns Sjukvårdsområde, Region Stockholm |
| Principal Investigator |
| Studieenheten, Akademiskt Specialistcentrum, Stockholm läns sjukvårdsområde, Region Stockholm | Recruiting | Stockholm | Sweden |
|
| Norrland University Hospital | Recruiting | Umeå | Sweden |
|
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D011164 | Porphyrias |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |