Spironolactone for Stroke Recovery
(REDUCE Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Yale University
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
The purpose of this research study is to determine whether blood pressure treatment regimens with spironolactone are better than blood pressure treatment regimens without spironolactone at lowering blood pressure in stroke survivors.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop taking your current medications. However, if you are on mineralocorticoid antagonist therapy, you may need to discontinue it for 3-12 months, depending on the investigator's discretion.
What data supports the idea that Spironolactone for Stroke Recovery is an effective drug?
The available research shows that Spironolactone can help reduce the size of brain damage after a stroke in rats. It improves the structure of blood vessels in the brain, which is important for recovery. In mice, Spironolactone also reduces harmful substances in the brain and increases helpful factors that protect brain cells and improve blood flow. This leads to a smaller area of damage in the brain. These findings suggest that Spironolactone may be effective in helping the brain recover after a stroke.12345
What safety data is available for spironolactone?
Spironolactone has been studied for various conditions, including resistant hypertension, pediatric cardiology, and hirsutism. It is known to have antiandrogenic effects and can cause side effects like hyperkalemia. In pediatric cardiology, careful monitoring of electrolytes is recommended. It should be avoided during pregnancy and in women with a family history of breast cancer. New derivatives like SC 23992 show potential for fewer side effects.46789
Is the drug Spironolactone a promising treatment for stroke recovery?
Eligibility Criteria
This trial is for adults over 18 who've had a stroke confirmed by CT or MRI, or have persistent symptoms of ischemic injury. They must be able to follow the study plan and not be pregnant, breastfeeding, or planning pregnancy. People with life expectancy under a year, severe kidney issues, high potassium levels, large upper arm circumference (>17 inches), extreme blood pressure values, Addison's disease or allergies to spironolactone can't join.Inclusion Criteria
Written, informed consent by patient or surrogate
I have had a stroke or brain bleed confirmed by a scan.
Ability to comply with all study procedures and available for the duration of the study
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Exclusion Criteria
Pregnancy, planned pregnancy, or breastfeeding
You are not expected to live for more than 1 year.
Your blood test results showed high levels of potassium on two recent tests before joining the study.
See 9 more
Treatment Details
Interventions
- Spironolactone (Diuretic)
Trial OverviewThe study is testing if adding the pill spironolactone to regular blood pressure treatments helps better control blood pressure in people recovering from strokes compared to standard treatment without it.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: SpironolactoneExperimental Treatment1 Intervention
Participants randomized to the Spironolactone arm will be receiving Spironolactone in addition to their normal routine blood pressure treatment.
Group II: Standard CareActive Control1 Intervention
Participants randomized to the Standard care arm will be receiving their normal routine blood pressure treatment.
Spironolactone is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Aldactone for:
- High blood pressure
- Heart failure
- Liver scarring
- Kidney disease
- Low blood potassium
- Early puberty in boys
- Acne
- Excessive hair growth in women
🇪🇺 Approved in European Union as Aldactone for:
- Fluid retention due to heart failure
- Liver scarring
- Kidney disease
- High blood pressure
- Low blood potassium
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Wake Forest Baptist HealthWinston-Salem, NC
University of Texas Health Science Center at HoustonHouston, TX
Temple University HospitalPhiladelphia, PA
Yale New Haven HospitalNew Haven, CT
More Trial Locations
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
American Heart AssociationCollaborator
References
Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats. [2018]Previous studies show that ischemic cerebral infarct size is related to cerebral vessel structure. Spironolactone, a mineralocorticoid receptor antagonist, decreases ischemic cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that chronic spironolactone treatment would improve cerebral artery structure in the SHRSP.
The role of mineralocorticoid receptor expression in brain remodeling after cerebral ischemia. [2021]Mineralocorticoid receptors (MRs) are classically known to be expressed in the distal collecting duct of the kidney. Recently it was reported that MR is identified in the heart and vasculature. Although MR expression is also found in the brain, it is restricted to the hippocampus and cerebral cortex under normal condition, and the role played by MRs in brain remodeling after cerebral ischemia remains unclear. In the present study, we used the mouse 20-min middle cerebral artery occlusion model to examine the time course of MR expression and activity in the ischemic brain. We found that MR-positive cells remarkably increased in the ischemic striatum, in which MR expression is not observed under normal conditions, during the acute and, especially, subacute phases after stroke and that the majority of MR-expressing cells were astrocytes that migrated to the ischemic core. Treatment with the MR antagonist spironolactone markedly suppressed superoxide production within the infarct area during this period. Quantitative real-time RT-PCR revealed that spironolactone stimulated the expression of neuroprotective or angiogenic factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), whereas immunohistochemical analysis showed astrocytes to be cells expressing bFGF and VEGF. Thereby the incidence of apoptosis was reduced. The up-regulated bFGF and VEGF expression also appeared to promote endogenous angiogenesis and blood flow within the infarct area and to increase the number of neuroblasts migrating toward the ischemic striatum. By these beneficial effects, the infarct volume was significantly reduced in spironolactone-treated mice. Spironolactone may thus provide therapeutic neuroprotective effects in the ischemic brain after stroke.
The spironolactone renaissance. [2019]Until recently, spironolactone was considered only as an antagonist at the aldosterone receptors of the epithelial cells of the kidney and was used clinically in the treatment of hyperaldosteronism and, occasionally, as a K(+)-sparing diuretic. The spironolactone renaissance started with the experimental finding that spironolactone reversed aldosterone-induced cardiac fibrosis by a cardiac action. Experimentally, spironolactone also has direct effects on blood vessels. Spironolactone reduces vascular fibrosis and injury, inhibits angiogenesis, reduces vascular tone and reduces portal hypertension. The rationale for the Randomized Aldactone Evaluation Study (RALES) of spironolactone in heart failure was that 'aldosterone escape' occurred through non-angiotensin II mechanisms. The RALES clinical trial was stopped early when it was shown that there was a 30% reduction in risk of death among the spironolactone patients. In RALES, spironolactone also reduced hospitalisation for worsening heart failure and improved the symptoms of heart failure. Other recent clinical trials have shown that spironolactone reduces cardiac and vascular collagen turnover, improves heart variability, reduces ventricular arrhythmias, improves endothelial dysfunction and dilates blood vessels in human heart failure and these effects probably all contribute to the increased survival in heart failure. Spironolactone may also be useful in the treatment of left ventricular hypertrophy, portal hypertension and cirrhosis. There have also been some recent small clinical trials of spironolactone as an anti-androgen showing potential in acne, hirsutism and precocious puberty.
Spironolactone management of resistant hypertension. [2013]To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone in the treatment of resistant hypertension.
Pituitary-thyroid function in spironolactone treated hypertensive women. [2019]Four weeks high dose spironolactone treatment (Aldactone Searle, 100 mg q. i. d.) significantly enhanced the TSH (delta max. 8.5 +/- 4.1 vs. 4.6 +/- 3.1 microunits/ml, P less than 0.05) and T3 (delta max. 32 +/- 27 vs. 11 +/- 16 ng/100 ml, P less than 0.05) responses to an intravenous TRH/LH-RH bolus injection in 6 eumenorrhoeic euthyroid hypertensive women, without affecting basal serum TSH, T3 or T4 levels or the basal and stimulated LH, FSH and prolactin values (P greater than 0.10). The mean serum testosterone, 17-hydroxyprogesterone and oestradiol levels were also similar before and during therapy. Spironolactone, possibly by virtue of its antiandrogenic action, may exert its enhancing effect on pituitary-thyroid function by modulating the levels of receptors for TRH in the thyrotrophs or by altering the T3 receptor in the pituitary permitting a greater response to TRH.
Aldosterone antagonists. 3. Synthesis and activities of steroidal 7 alpha-(alkoxycarbonyl)-15,16-methylene spirolactones. [2019]Several A- and D-ring substituted steroidal 7 alpha-alkoxycarbonyl spirolactones were synthesized with the purpose of increasing the aldosterone antagonistic potency and reducing the endocrinological side effects relative to the standard drug spironolactone. It was found that the 15 beta,16 beta-methylene derivative 17 exhibited a 2-fold higher aldosterone antagonistic activity compared to either spironolactone or the 15,16-unsubstituted derivative 29 while showing remarkably reduced antiandrogenicity.
[Experiences with aldactone in pediatric cardiology (author's transl)]. [2013]In Pediatric Cardiology for many years the usage of spironolactone (Aldactone) and Canreonat-K+ (Aldactone pro injectione) had been experienced. The efficiency of aldactone was controlled by clinical parameters, electrolytes, discontinuity of the drug and in some cases by radioimmunologic measurement of the plasma aldosterone concentration. The treatment with aldactone in combination with digitalis gave good clinical results in cases with and without signs of secondary hyperaldosteronism. The recommended dosage i. v. and orally was for infancy 2--3 mg/kg/die the first 2--4 days and afterwards 1,5--2 mg/kg/die, for later childhood 4--5 mg/kg/die for 3--5 days and afterwards 2--3 mg/kg/die. Special attention should be paid to hyperkaliemia, over 6 mval serum K+ the aldactone administration was interrupted.
SC 23992: radioreceptor assays for therapeutic and side effects. [2019]1. A new spirolactone (SC 23992) has been assayed in vitro to determine its affinity for mineralocorticoid and androgen receptors. 2. Although two to eight times as potent as anti-aldosterone agent as Aldactone in vivo, SC 23992 has only approximately 10% the potency in vitro. 3. This discrepancy between potency in vivo and in vitro appears to be explained on radioreceptor assay of the principal metabolites of Aldactone SC 23992. 4. SC 23992 may represent an antimineralocorticoid with less antiandrogen side effects.
Use of spironolactone in treatment of hirsutism. [2019]Spironolactone (Aldactone), 100 mg to 200 mg daily, has antiandrogenic effects that may enhance treatment of androgen-excess syndromes, particularly severe hirsutism. Combination therapy with an oral contraceptive or with dexamethasone appears to have a beneficial effect. Side effects are transient. The drug should be avoided during pregnancy and in women who have a family history of breast cancer, although there is no proven association between spironolactone and breast malignancy.
Spironolactone in dermatology: uses in acne and beyond. [2021]Spironolactone is a synthetic aldosterone receptor antagonist, with a role off-label in various dermatological conditions. Its antiandrogenic properties make it suitable for diseases in which excess androgen production results in unwanted and psychologically distressing manifestations in susceptible females. Treatment with spironolactone aims to attenuate androgen-mediated conditions including acne, hidradenitis suppurativa, female pattern hair loss and hirsutism. We discuss the emerging utility of spironolactone in dermatology, its potential adverse effects and considerations for monitoring.