None listed
Conditions
Brief summary
Lithium is first line treatment for acute and maintenance of bipolar affective disorder, and as augmentation for refractory major depression. The most prevalent renal effect of lithium is impairment of renal concentrating ability, which may affect at least half of all patients on chronic lithium treatment. Up to 20% of patients will report polydipsia and polyuria as a result of this change. If lithium is stopped early on, the decreased urinary concentrating ability is largely reversible. However some patients who remain on lithium long term, will develop a progressive impairment of urinary concentrating ability [nephrogenic diabetes insipidus]. This functional lesion is not usually reversible and is associated with a chronic focal interstitial fibrosis in renal biopsy, which may be progressive and lead to end-stage renal failure. Amiloride is a potassium-sparing diuretic that in clinical case series can reverse lithium-induced polyuria and improve renal concentrating ability. Mechanistically, amiloride blocks the renal epithelial sodium channel, which is the major entry site for lithium in collecting duct cells. Although combining amiloride with lithium could reduce development of lithium-induced renal toxicity, it is unclear what the optimal dose of both drugs might be. Earlier studies have used 10mg/day (Bedford 2008), or 10-20mg/day (Batlle 1985, Kosten 1986). The objective of this study is to evaluate the pharmacodynamic interaction between 2 dose levels of amiloride (5 and 10mg/day) and 2 dose levels of lithium (250 and 500mg/day), based on changes in renal concentrating ability.
Interventions
From day 2, volunteers will receive either oral tablets of lithium 250mg or 500mg/day for 8 weeks. In addition, during weeks 5-6, they will also receive oral tablets of amiloride 5mg/day, and during weeks 7-8, they will receive amiloride 10mg/day. The volunteers will be seen weekly to assess adherence by tablet count.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Capable of understanding and signing an informed consent. 2. Aged >18 years on the day of consent. 3. Good general health. 4. Suitable venous access.
Exclusion criteria
1. Females who are or intend to become pregnant, or are lactating. 2. Participants who, in the opinion of the investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved). 3. Any participant for whom the investigator believes, for any reason, that participation would not be an acceptable risk. 4. Alcohol abuse, or regular use of cannabis or other recreational drugs. 5. Patients established on diuretics or regularly taking NSAIDs.
Outcome results
None listed