Clinical trial NCT02236598: The Effects of Potassium on Glucose Metabolism in African Americans
Official title: The Effects of Potassium on Glucose Metabolism in African Americans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Borderline Hypokalemia
Keywords: borderline hypokalemia
glucose tolerance
insulin secretion
insulin sensitivity
fasting glucose
African American
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2014-09-10
Enrollment: 61
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: African Americans suffer a disproportionately high risk of diabetes compared to other Americans. Reasons for race disparities in diabetes incidence are not completely understood. Although a difference in prevalence of obesity does explain a significant portion of the racial disparity in diabetes risk, it does not explain all of this disparity. Strategies to control the diabetes epidemic and reduce its racial disparity often overlook preventive measures. Currently, the most powerful known strategy for preventing diabetes is weight loss in the overweight/obese. However, because weight loss is often difficult to achieve and maintain, other opportunities to prevent diabetes should be identified, particularly in African Americans. Among potential novel opportunities is correction of low or low-normal potassium levels (hypokalemia). In secondary analyses, we have found low-normal potassium (K) to be a novel risk factor for diabetes; and we have found that this association between low-K and diabetes risk may be stronger in African Americans compared to whites. Therefore, a previously unrecognized alternative or adjunct strategy for preventing diabetes, particularly in African Americans, may involve correction of low or low-normal K levels (hypokalemia). Large-scale, adequately-powered, randomized controlled trials are needed to establish the effectiveness of this approach. However, prior to those trials, the pathophysiology of the association between low K and poor glucose metabolism must be understood. This pilot clinical trial will begin to determine the effect of K supplementation on measures of glucose metabolism in African Americans.

In this pilot clinical trial, 30 African Americans with prediabetes and a low-normal serum K \[\<4.0 milliequivalent/Liter (Eq/L)\] will be randomized to K-supplements, 20mEq (2-10mEq tablets) twice daily or a matching placebo capsules twice daily. Prior to randomization, baseline measures will be taken including measures of glucose metabolism with a 3-hour oral glucose tolerance test (OGTT), baseline chemistries and a baseline 24-hour urinary potassium measurement. Patients will take the intervention daily and will undergo repeat testing of all of these measures at the end of a 3 month period. The primary endpoint will be change in glucose tolerance, as measured by change in glucose area-under-the-curve (AUC) of a 3-hour oral glucose tolerance test (OGTT). Secondary endpoints will include changes in fasting, 1-hour, and 2-hour post-challenge glucose levels, as well as measurements of insulin secretion and insulin sensitivity as measures by the oral glucose minimal model method.(1) The baseline data from this trial will allow us to quantify abnormalities in glucose metabolism in African Americans with prediabetes/early diabetes and low-normal serum K. The post-intervention data will provide estimates of the impact of K-supplements compared to no supplements on these abnormalities. Data derived from the pilot study will be used in the design of a larger scale, adequately powered clinical trial. This trial will also help to assess the feasibility of recruiting this target population.

With this pilot trial, we will begin to determine whether or not K-supplements, an inexpensive, well-tolerated, and simple intervention, could help to reduce diabetes risk among African Americans.


Eligibility criteria: Inclusion Criteria:

To be eligible for inclusion in the study the following enrollment criteria must be met:

1. Participants must be 30 years of age or older.
2. They must have a diagnosis of prediabetes defined as a hemoglobin A1c between 5.7-6.5% measured at the initial screening visit.
3. They must have a serum K+ of 3.3-4.0 mEq/L on 2 occasions, within a 18 month period, including at initial screening visit. If subject is just outside range for inclusion, PI may offer the subject the option to repeat their screening serum K+ measurement.
4. The participant must be willing and capable of providing written informed consent.
5. The participant must be available for follow-up and must at minimum have telephone access.
6. Participants must be able to read/understand English.

Exclusion Criteria:

* Participants must not have any of the following:

  1. Participants must not have evidence of chronic kidney disease with an estimated Glomerular Filtration Rate (eGFR) \< 60ml/min. All patients will be screened for eGFR at the enrollment visit.
  2. Participants must not have evidence of diabetes mellitus requiring treatment with medications prior to screening visit. The cannot have a random or post-challenge glucose ≥ 200mg/dl (from prior labs), A1c level ≥ 6.5% (from prior labs), prior physician diagnosis, or use of anti-diabetic medications. If participants have glucose levels in the diabetic range at screening visit, they will be eligible to continue in study as long as glucose levels are not \> 200 mg/dl.
  3. Participants must not have a history of endoscopy-verified peptic ulcer disease with past history of either gastric or duodenal ulcer.
  4. Participants must not have evidence of cardiac arrhythmias, unstable angina or cardiac event within 6 months, congestive heart failure, or other conditions that might impact follow-up, based on the discretion of the principal investigator.
  5. Participants must not be pregnant or intend to get pregnant during the study period. The study intervention is safe for pregnant women, so serum pregnancy screening is not indicated; however, pregnant women are excluded because pregnancy affects glucose homeostasis, which will bias primary outcome measurement and damage scientific validity of the study.

Primary outcomes:
measure: Change in Glucose Tolerance as Measured by Area-under-the-curve
timeFrame: Baseline to 3 months
Secondary outcomes:
measure: Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL
timeFrame: Baseline to 3 months
measure: Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC)
timeFrame: Baseline to 3 months
measure: Changes in Insulin Sensitivity
timeFrame: Baseline to 3 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Ranee C Montgomery, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chatterjee R, Davenport CA, Kwee L, D'Alessio D, Svetkey LP, Lin PH, Slentz CA, Ilkayeva O, Johnson J, Edelman D, Shah SH. Preliminary evidence of effects of potassium chloride on a metabolomic path to diabetes and cardiovascular disease. Metabolomics. 2020 Jun 18;16(7):75. doi: 10.1007/s11306-020-01696-w.
citation: Chatterjee R, Slentz C, Davenport CA, Johnson J, Lin PH, Muehlbauer M, D'Alessio D, Svetkey LP, Edelman D. Effects of potassium supplements on glucose metabolism in African Americans with prediabetes: a pilot trial. Am J Clin Nutr. 2017 Dec;106(6):1431-1438. doi: 10.3945/ajcn.117.161570. Epub 2017 Nov 1.