Polycythemia
Conditions
Brief summary
The purpose of this study is to evaluate the effect of the (angiotensin-converting enzyme) ACE inhibitor lisinopril on hemoglobin, hematocrit, and erythropoietin levels in patients with secondary polycythemia due to high-oxygen-affinity hemoglobin variants, oxygen-sensing pathway mutations, or other unexplained and potentially irreversible forms of erythrocytosis. This study aims to determine whether ACE inhibition can effectively reduce excessive erythrocytosis by modulating erythropoietin production.
Detailed description
Demonstrating that ACE inhibitor therapy with lisinopril lowers hemoglobin, hematocrit, and erythropoietin levels could introduce a novel therapeutic approach for the management of secondary polycythemia due to high-oxygen-affinity hemoglobin variants, oxygen-sensing pathway mutations, or other unexplained and potentially irreversible forms of erythrocytosis, potentially reducing reliance on repeated phlebotomies and lowering thrombotic risk.
Interventions
Subjects will be treated with Lisinopril in three phases: Phase 1: Baseline-3 weeks: 2.5 mg dose Phase 2: Weeks 4 - 7: 5 mg dose (2 x 2.5mg tablets) Phase 3: Weeks 8-12: 10 mg dose (4 x 2.5 mg tablets)
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Hemoglobin in Men: \>16.5 g/dL (10.3 mmol/L). * Hemoglobin in Women \>16.0 g/dL (10.0 mmol/L). * BMI 18-40 kg/m2.
Exclusion criteria
* Positive JAK2 gene linked to Polycythemia Vera. * Current smoker or previous heavy smoker (\>15 pack years) who quit less than 12 months prior to enrollment. * Resting SpO₂ ≤ 94% on room air. * Current or recent (within the past 6 months) use of testosterone or androgen supplementation. * Any confounding respiratory or renal disease, including diagnosed or suspected sleep apnea, or stage 3 and up of chronic kidney disease. * Any confounding hematologic disease that may alter hemoglobin level. * Currently treated with ACE inhibitors. * Currently treated with potassium-sparing diuretics. * Currently on SGLT2 or use within 4 weeks prior to screening. * Baseline systolic blood pressure ≤90 mmHg. * Baseline systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg. * Occupational exposure associated with chronically elevated COHb (auto repair, etc.). * History of anaphylaxis or angioedema. * Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hemoglobin | Baseline (dose 0), study day 3 (dose 2.5), study day 5 (dose 5.0), and study day 7 (dose 10.0) | Hemoglobin measures the amount of a protein in red blood cells via blood sample and is reported in grams per deciliter (g/DL) Hemoglobin (Hb) concentration exceeding 16 g/dL in women and 16.5 g/dL in men is considered abnormal. |
| Change in hematocrit | Baseline (dose 0), study day 3 (dose 2.5), study day 5 (dose 5.0), and study day 7 (dose 10.0) | Hematocrit (Hct) is measured by determining the percentage of red blood cells (RBCs) in a blood sample. Hematocrit (Hct) ≥ 48% in women and ≥49% in men is considered elevated. |
| Change in erythropoietin | Baseline (dose 0), study day 3 (dose 2.5), study day 5 (dose 5.0), and study day 7 (dose 10.0) | Erythropoietin is measured via blood test to detect hormone levels, and is reported in milliunits per milliliter (mU/mL). A normal reference range is generally 4 to 26 mU/mL) |
Countries
United States
Contacts
CONTACTNancy Meyer
PRINCIPAL_INVESTIGATORMichael Joyner, MD
Mayo Clinic
Outcome results
None listed