The Effect Of Lisinopril On Polycythemia

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Polycythemia
• Intervention / Treatment: Drug: Lisinopril Tablets

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nancy Meyer; Phone Number: 507-255-0913

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lisinopril; Patients diagnosed with polycythemia will be treated with Lisinopril, 2.5 mg tablets	Drug: Lisinopril Tablets; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin	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.	Baseline (dose 0), study day 3 (dose 2.5), study day 5 (dose 5.0), and study day 7 (dose 10.0)
Change in hematocrit	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.	Baseline (dose 0), study day 3 (dose 2.5), study day 5 (dose 5.0), and study day 7 (dose 10.0)
Change in erythropoietin	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)	Baseline (dose 0), study day 3 (dose 2.5), study day 5 (dose 5.0), and study day 7 (dose 10.0)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael Joyner, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Hemic and Lymphatic Diseases; Polycythemia; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Dipeptides; Lisinopril
• Other Study ID Numbers: 26-003687

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No