A double‐blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent β‐thalassemia patients

Karami, Hossein; Arjmandi, Hadiseh Khalilzadeh; Salehifar, Ebrahim; Darvishi‐Khezri, Hadi; Dabirian, Mojdeh; Kosaryan, Mehrnoush; Aliasgharian, Aily; Akbarzadeh, Rosetta; Aali, Raheleh Naeimayi; Nasirzadeh, Amirreza

doi:10.1111/ijcp.14337

Cited by 4 publications

(9 citation statements)

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“…All outcomes were evaluated at 6 and 12 months, depending on which was reported in the study. The study (Karami et al 16 ) was a cross‐over study with two groups: The AP sequence and the PA sequence. In the AP sequence, amlodipine was used for 6 months, followed by a placebo for another 6 months.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta‐analysis with trial sequential analysis

Soliman

Abdelaziz

Mouffokes

et al. 2023

European J of Haematology

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Objectives Iron overload in patients with thalassemia represents a serious complication by affecting numerous organ systems. This meta‐analysis aims to establish an evidence regarding the effect of amlodipine on cardiac iron overload in thalassemia patients. Methods We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials (RCTs). The primary outcomes were cardiac T2* and myocardial iron concentration (MIC). Secondary outcomes were liver iron concentration (LIC), risk of Gastrointestinal (G.I.) upset and risk of lower limb edema. We used Hedges' g to pool continuous outcomes, while odds ratio was used for dichotomous outcomes. Results Seven RCTs were eligible for this systematic review and meta‐analysis, comprising of 233 patients included in the analysis. Amlodipine had a statistically significant lower MIC (Hedges' g = −0.82, 95% confidence interval [CI] [−1.40, −0.24], p < .001) and higher cardiac T2* (Hedges' g = 0.36, 95% CI [0.10, 0.62], p = .03). Amlodipine was comparable to standard chelation therapy in terms of the risk of lower limb edema and GI upset. Conclusion Our meta‐analysis found that amlodipine significantly increases cardiac T2* and decreases MIC, hence decreasing the incidence of cardiomyopathy‐related iron overload in thalassemia patients.

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Section: Methodsmentioning

confidence: 99%

Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta‐analysis with trial sequential analysis

Soliman

Abdelaziz

Mouffokes

et al. 2023

European J of Haematology

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“…In psoriasis, it has been shown that external antigen triggers innate immunity and activates plasmacytoid dendritic cells, which produce IL-23 and TNF-alpha to differentiate naive T cells into Th17 cells. Then Th17 cells produce IL-17 to promote epidermal proliferation [1][2][3]. The basal cell responds to IL-17 stimuli for proliferation and differentiation to produce a thickened epidermis.…”

Section: Metabolic Competition Maintains Hyperproliferation Of Epider...mentioning

confidence: 99%

“…Psoriasis is one of the most common chronic immune-mediated skin diseases with an estimated global prevalence of 2-3% 1 - 3 . It is primarily a disease in which the skin barrier is compromised due to the destabilization of cell proliferation and differentiation 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Energy competition remodels the metabolic glucose landscape of psoriatic epidermal cells

Liu,

Jiang,

et al. 2024

Theranostics

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Rationale: Skin cells actively metabolize nutrients to ensure cell proliferation and differentiation. Psoriasis is an immune-disorder-related skin disease with hyperproliferation in epidermal keratinocytes and is increasingly recognized to be associated with metabolic disturbance. However, the metabolic adaptations and underlying mechanisms of epidermal hyperproliferation in psoriatic skin remain largely unknown. Here, we explored the role of metabolic competition in epidermal cell proliferation and differentiation in psoriatic skin. Methods: Bulk- and single-cell RNA-sequencing, spatial transcriptomics, and glucose uptake experiments were used to analyze the metabolic differences in epidermal cells in psoriasis. Functional validation in vivo and in vitro was done using imiquimod-like mouse models and inflammatory organoid models. Results: We observed the highly proliferative basal cells in psoriasis act as the winners of the metabolic competition to uptake glucose from suprabasal cells. Using single-cell metabolic analysis, we found that the "winner cells" promote OXPHOS pathway upregulation by COX7B and lead to increased ROS through glucose metabolism, thereby promoting the hyperproliferation of basal cells in psoriasis. Also, to prevent toxic damage from ROS, basal cells activate the glutathione metabolic pathway to increase their antioxidant capacity to assist in psoriasis progression. We further found that COX7B promotes psoriasis development by modulating the activity of the PPAR signaling pathway by bulk RNA-seq analysis. We also observed glucose starvation and high expression of SLC7A11 that causes suprabasal cell disulfide stress and affects the actin cytoskeleton, leading to immature differentiation of suprabasal cells in psoriatic skin. Conclusion: Our study demonstrates the essential role of cellular metabolic competition for skin tissue homeostasis.

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“…Amlodipine is a dihydropyridine-type calcium blocker that may impede calcium influx. Amlodipine is available at a lower price, with oral administration, proven safety, and a long half-life (35 to 50 h) [5,17]. Some clinical trials have shown the significant impacts of amlodipine on reducing iron overload.…”

Section: Introductionmentioning

confidence: 99%

“…Some clinical trials have shown the significant impacts of amlodipine on reducing iron overload. The lack of sample size in the prior studies on β-thalassemia cases necessitates conducting a review on this issue [4,5,17,18].…”

Section: Introductionmentioning

confidence: 99%

Amlodipine Therapy in β-Thalassemia Patients: A Systematic Review and Meta-Analysis on Ferritin Levels and Liver MRI T2*

Aliasgharian,

Karami,

Zahedi

et al. 2023

Thalassemia Reports

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Background and aim: We conducted a review to determine the efficacy of amlodipine alongside iron chelators on serum ferritin levels and liver T2-weighted magnetic resonance imaging (MRI T2*) in β-thalassemia patients. Methods: Systematic search was conducted in multiple databases, including Web of Science, PubMed, Scopus, Embase, Cochrane Library, ClinicalTrials.gov, the Iranian Registry of Clinical Trials (IRCT), ProQuest, OpenGrey, and Web of Science Conference Proceedings Citation Index. The search was closed in January 2023. Primary outcomes were comprised of liver MRI T2* (millisecond (msec)) and serum ferritin levels (ng/mL). Results: Seven studies (n = 227) were included in the study. The pooled Cohen’s d for serum ferritin was estimated at −0.46, 95% confidence interval (CI) −1.11 to 0.19 and p = 0.16 (I2 86.23%, p < 0.0001). The pooled mean difference for serum ferritin was −366.44 ng/mL, 95% CI −844.94 to 112.05, and p = 0.13 (I2 81.63%, p < 0.0001). After a meta-regression based on the length of using amlodipine, a coefficient for the mean difference was also −23.23 ng/mL and 95% CI −155.21 to 108.75. The coefficient obtained from a meta-regression as per the amlodipine dose at 5 mg/day than 2.5 to 5 mg/day anchored at −323.49 ng/mL and 95% CI −826.14 to 1473.12. A meta-regression according to the baseline values of serum ferritin discovered a coefficient of 1.25 ng/mL and 95% CI 0.15 to 2.35. Based on two included studies (n = 96), the overall Cohen’s d for liver MRI T2* was 2.069, 95% CI −0.896 to 5.035, and p = 0.17 (I2 96.31%, p< 0.0001). The synthesized mean difference for liver MRI T2* was 8.76 msec, 95% CI −4.16 to 21.67, and p = 0.18 (I2 98.38%, p < 0.000). Conclusion: At a very low level of evidence, probably using amlodipine at a dose of 2.5 to 5 mg a day, up to a year, alongside iron chelators slightly decreases serum ferritin levels in iron-overloaded thalassemia cases by nearly 366 ng/mL (23 ng/mL per month). The liver MRI T2* might also rise to 8.76 msec upon co-therapy with amlodipine.

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A double‐blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent β‐thalassemia patients

Cited by 4 publications

References 38 publications

Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta‐analysis with trial sequential analysis

Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta‐analysis with trial sequential analysis

Energy competition remodels the metabolic glucose landscape of psoriatic epidermal cells

Amlodipine Therapy in β-Thalassemia Patients: A Systematic Review and Meta-Analysis on Ferritin Levels and Liver MRI T2*

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