Metformin as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 12/22/2018 |
| Start Date: | June 27, 2016 |
| End Date: | December 30, 2020 |
This study will test to see if metformin is safe and if it is tolerated compared to placebo
in adult Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with beginning stages
of chronic kidney disease. We will also measure its effect on progression of kidney disease
as reflected in the kidney size and the kidney function, along with its effect on kidney pain
and quality of life.
in adult Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with beginning stages
of chronic kidney disease. We will also measure its effect on progression of kidney disease
as reflected in the kidney size and the kidney function, along with its effect on kidney pain
and quality of life.
There is growing evidence that metformin, a drug widely used for the treatment of type 2
diabetes and polycystic ovary syndrome, may serve as a novel therapy for individuals in the
early stages of Autosomal Dominant Polycystic Kidney Disease ADPKD by activating the
metabolic sensor AMP-activated protein kinase (AMPK). AMPK is activated under conditions of
metabolic and other cellular stresses. Through its actions on downstream mediators, AMPK
activation during low energy states decreases cellular energy consumption while stimulating
energy generating pathways. It has been shown that AMPK phosphorylates and inhibits cystic
fibrosis transmembrane conductance regulator (CFTR), thus suppressing epithelial fluid and
electrolyte secretion. Similarly, AMPK phosphorylates the tuberin protein, leading to
indirect inhibition of the mTOR pathway. Thus, AMPK inhibits both CFTR and mTOR, suggesting
that targeted activation of this kinase by metformin may provide a therapeutic benefit in
ADPKD. It has been shown that metformin treatment of kidney epithelial cells leads to
stimulation of AMPK and subsequent inhibition of both mTOR and CFTR activity. It has also
been shown that metformin slows cystogenesis in animal models of PKD, supporting the
potential of this drug in ADPKD treatment.
diabetes and polycystic ovary syndrome, may serve as a novel therapy for individuals in the
early stages of Autosomal Dominant Polycystic Kidney Disease ADPKD by activating the
metabolic sensor AMP-activated protein kinase (AMPK). AMPK is activated under conditions of
metabolic and other cellular stresses. Through its actions on downstream mediators, AMPK
activation during low energy states decreases cellular energy consumption while stimulating
energy generating pathways. It has been shown that AMPK phosphorylates and inhibits cystic
fibrosis transmembrane conductance regulator (CFTR), thus suppressing epithelial fluid and
electrolyte secretion. Similarly, AMPK phosphorylates the tuberin protein, leading to
indirect inhibition of the mTOR pathway. Thus, AMPK inhibits both CFTR and mTOR, suggesting
that targeted activation of this kinase by metformin may provide a therapeutic benefit in
ADPKD. It has been shown that metformin treatment of kidney epithelial cells leads to
stimulation of AMPK and subsequent inhibition of both mTOR and CFTR activity. It has also
been shown that metformin slows cystogenesis in animal models of PKD, supporting the
potential of this drug in ADPKD treatment.
Inclusion Criteria:
Subject has Autosomal Dominant Polycystic Kidney Disease; Subject is fluent in English
Exclusion Criteria:
Subject is not on active military duty; Subject is not currently participating in another
clinical trial; Subject's current GFR is not <50 cc/min/1.73m2; Subject does not have
diabetes; Subject does not have a systemic disease other than hypertension and PKD; Subject
does not have a solitary kidney; Subject does not have an allergy or intolerance to
metformin; Subject is not pregnant or lactating or intending to become pregnant within the
next three years; Subject does not have an unstable or unclipped cerebral aneurysm; Subject
does not have active coronary artery disease; Subject does not have an MRI incompatible
device/implant; Subject does not have severe claustrophobia; Subject has not had any solid
organ transplant; Subject does not have a Vitamin B12 deficiency; Subject does not
currently take any medications that interact with metformin, such as nifedipine,
furosemide, cationic drugs (amiloride, ranitidine, triamterene digoxin, procainamide,
quinidine, vancomycin, trimethoprim); Subject does not currently take nor has taken (within
2 weeks) the drug tolvaptan (Jynarque or Samsca)
We found this trial at
2
sites
22 S Greene St
Baltimore, Maryland 21201
Baltimore, Maryland 21201
(410) 328-8667
Principal Investigator: Terry Watnick, MD
Phone: 410-328-0207
University of Maryland Medical Center Founded in 1823 as the Baltimore Infirmary, the University of...
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800 Washington St
Boston, Massachusetts 02111
Boston, Massachusetts 02111
(617) 636-5000
Principal Investigator: Ronald Perrone, MD
Phone: 617-636-8117
Tufts Medical Center Tufts Medical Center is an internationally-respected academic medical center – a teaching...
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