Acute Effects of Canagliflozin, a Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor on Bone Metabolism in Healthy Volunteers

NCT02404870 | Completed Phase 1 FDA Drug

• 2 other identifiers: 14019514-DK-0195
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Canagliflozin (sold as InvokanaTM) is a new medicine for diabetes. But it might increase the bone fracture risk in people with diabetes. Objective: \- To see if Invokana has negative side effects on bone health. Eligibility: \- Healthy men ages 18 45. Design:

• Participants will be screened with a medical history, physical exam, and blood tests. A nutritionist will discuss their dietary history and the study dietary requirements. Participants will get a food diary to record what they eat and drink on 3 separate days.
• Participants will have a DEXA scan x-ray test of bone health. Participants will lie still on a table while a small camera passes over the body.
• Participants will have 2 stays in the clinic. They will be 1 week apart and each last 6 overnights starting on a Sunday.
• Before each stay, participants will:
• Pick up food each day for 7 days. They will get breakfast, lunch, dinner, and snacks. They must eat only the food provided during these times.
• Collect their urine twice.
• During the stays, participants will:
• Be evaluated by a doctor and have blood drawn.
• On each Monday, participants will:
• Skip breakfast
• At about 8 a.m. take a placebo pill in one stay, the study drug in the other stay.
• Drink 6 ounces of water every 2 hours for 4 hours.
• An intravenous (IV) catheter will be inserted into an arm. Blood will be drawn every 2 hours from 8 a.m. until noon.
• Get lunch.
• Have blood testing again at 8pm and midnight.
• Repeat the testing days 2 5.
• Have urine collected.

Conditions

Healthy Volunteers

Keywords

Diabetes; Phosphate; Fibroblast Growth Factor 23 (FGF23); Vitamin D; PTH

Outcome Measures

Primary Outcomes (1)

• AUC of FGF23

  In this study, our primary endpoint is the area under the curve (AUC) for FGF23 for the 24-72 hours from the first day of administration of canagliflozin. The null hypothesis is that there will be no change in the mean 24-72 hours AUC of FGF23 after the treatment compared with the mean baseline value. We acknowledge that the magnitude and time course of changes (if any) in FGF23 are totally unknown.

  First 24-72 hours

Secondary Outcomes (4)

• FGF23 peack or AUC

  12 hours

• Transtubular reabsorption of phosphate

  12 hours

• PTH

  12 hours

• 1, 25 vitamin D

  12 hours

Study Arms (2)

Admission 1 or 2

EXPERIMENTAL

Canagliflozin

Drug: Canagliflozin

Admission 2 or 1

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

Placebo

Admission 2 or 1

Canagliflozin DRUG

Canagliflozin is a new oral drug for the treatment of type 2 diabetes mellitus (T2DM), and is one of two recently FDA approved sodium glucose co-transporter 2 (SGLT2) inhibitors, which target renal glucose reabsorption and offer promising improvement in HbA1C.

Admission 1 or 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• We are targeting healthy men and women greater than or equal to 18 years old, inclusive of all races and ethnicity within a BMI of 20 30 kg/m(2). Specifically, we have defined healthy to mean: normal fasting glucose and hemoglobin A1c less than or equal to 6%, normal Hb, no glucosuria, normal renal function (based on normal serum creatinine + Cystatin C), urine albumin:creatinine ratio, protein:creatinine ratio, and GFR \> 80 as calculated by the CKD-Epi equation and normal lab urinalysis.

You may not qualify if:

• If you have any of the following health issues, you cannot participate in the study:
• Presence of heart disease, untreated high blood pressure (\>140/90 mm Hg), orthostatic hypotension or symptomatic hypotension, cancer, diabetes, recurrent symptomatic hypoglycemia and /or history of recurrent genital or urinary tract infection, thyroid disease, or any other condition that affects bone health
• Past history of eating disorder or psychiatric disorders, including severe depression, anxiety, or psychosis or presently on treatment with medications for any of these conditions
• Taking certain medications, especially those that affect bone metabolism (e.g., high dose vitamin D \[\>1000 units daily\] or calcium supplements \[\>800mg daily\], high dose vitamin A \[\>20,000 units daily\], phosphate binding antacids, calcitonin, calcitriol, growth hormone, or any anti-seizure medications for any reason including valproic acid, lamotrigine), certain medications for high blood pressure (diuretics), steroids including inhalers, diet/weight loss medications, or any other medications at the discretion of the principal investigator and/or study team
• Have started, increased or decreased calcium \[\>400mg daily\] or vitamin D \[\>1000 units daily\] supplements within 2 weeks of the study
• Dependence or regular use of alcohol (\>2 drinks per day), tobacco (smoking or chewing), amphetamines, cocaine, heroin or marijuana over the past 6 months
• Volunteers will be excluded if they have abnormal blood concentrations of
• inorganic phosphate level (less than or equal to 2.5 mg/dl or greater than or equal to 4.8 mg/dl),
• parathyroid hormone (PTH) (less than or equal to 60 pg/ml),
• creatinine (less than or equal to 1.5 mg/dl) or eGFR (\< 80 ml/min/1.73sq.m),
• fasting glucose (greater than or equal to 100 mg/dl),
• hemoglobin (less than or equal to 11 g/dl),
• liver function tests (more than twice normal),
• testosterone (less than or equal to 260 ng/dl)
• Participation in a vigorous exercise program (\>3h/day of vigorous activity)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Blau JE, Bauman V, Conway EM, Piaggi P, Walter MF, Wright EC, Bernstein S, Courville AB, Collins MT, Rother KI, Taylor SI. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight. 2018 Apr 19;3(8):e99123. doi: 10.1172/jci.insight.99123. eCollection 2018 Apr 19.

  PMID: 29669938 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Canagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Kelly B Roszko, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2015
• First Posted: April 1, 2015
• Study Start: September 16, 2014
• Primary Completion: May 1, 2019
• Study Completion: September 3, 2019
• Last Updated: March 4, 2025

Record last verified: 2025-03

Locations

US (1)