Clinical trial NCT06273644: Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment
Official title: Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Porphyria, Acute Intermittent
Lead sponsor: Nordlandssykehuset HF
Sponsor class: OTHER
Collaborators: name: University of Oslo
name: Nord University
name: UiT The Arctic University of Norway
name: Norwegian University of Science and Technology
name: The University of Texas Medical Branch, Galveston
First posted: 2024-02-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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, 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Urine Porphobilinogen/creatinine
timeFrame: 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
measure: Urine Porphobilinogen/creatinine concentration, percentage change of repeated measurements
timeFrame: Day 1 ,4, 8, 11, 15, 18, 22, 25 and 29 of Diet Intervention A and of Diet Intervention B
Secondary outcomes:
measure: Number of Hospitalizations,sick leaves, and doctor visits due to AIP
timeFrame: 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
measure: Health status
timeFrame: 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
measure: Plasma Glucose level
timeFrame: 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
measure: Interstitial fluid glucose level
timeFrame: Day 15 and 29 of diet A and day 15 and 29 of diet B
measure: Number of hypoglycemic events
timeFrame: Day 15 and 29 of diet A and day 15 and 29 of diet B
measure: Amino acid profile
timeFrame: 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
measure: Plasma insulin, glucose, c-peptide
timeFrame: 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
measure: HOMA score
timeFrame: 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
measure: HbA1c
timeFrame: 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
measure: Cytokines in plasma
timeFrame: 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
measure: Intestinal microbiota composition
timeFrame: 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
measure: Physical activity
timeFrame: Immediately after one week of Diet A, and immediately after one week of Diet B
measure: Blood pressure
timeFrame: 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
measure: Body composition, metabolic age
timeFrame: 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
measure: Mitochondrial oxygen consumption rate
timeFrame: 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
measure: ALAS1mRNA
timeFrame: 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
measure: Urine-ALA/creatinine & urine-porphyrins
timeFrame: 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
measure: Mitochondrial function-related genes
timeFrame: At baseline immediately before each participants first diet intervention
Other outcomes:
Locations:
city: Bodø
country: Norway
facility: Nordland Hospital Trust
state: Nordland
Study officials:
affiliation: Nordlandssykehuset HF
name: Elin Storjord, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: