Acarbose and Older Adults With Postprandial Hypotension (PPH)

The current proposal will determine if blocking carbohydrate intake in the small intestine with Acarbose can be a possible therapy for older adults with (PPH) Post Prandial Hypotension (a drop of blood pressure after eating), which can result in falls.

Study Overview

• Status: Completed
• Conditions: Syncope; Other Specified Hypotension
• Intervention / Treatment: Drug: Placebo; Drug: Acarbose

Detailed Description

Blocking the absorption of carbohydrates at the brush border of the small intestine with acarbose (an alpha-glucosidase inhibitor) seems a promising possibility as a potential therapeutic agent. Although designed as a second-line diabetes drug, this medication has very little risk of hypoglycemia in older adults. In fact the risk of hypoglycemia is extremely low even in patients concurrently taking concurrent hypoglycemia agents (including insulin), and there is almost no risk of hypoglycemia in subjects not on other diabetes medications. Acarbose suppresses postprandial glycemia by slowing small intestinal digestion and absorption of carbohydrate, and has been shown to slow gastric emptying Acarbose has yet to be examined in a prospective fashion in older adults, despite the prevalence of PPH in this patient population. Preliminary, pilot work done in our laboratory on older adults with PPH has demonstrated that the hypotensive response over 90 minutes to a standardized meal was significantly reduced by the administration of acarbose

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Coastal Health Research Institute, VGH Research Pavilion Room 186

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 63 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• be 65 years of age or older,
• be a non-smoker for at least 5 years
• be referred to the falls clinic at Vancouver General Hospital
• have a Folstein test of cognition > 25/30 to ensure meal log-book compliance

Exclusion Criteria:

• no oral or swallowing issues that would prevent a Meal Test
• subject requiring dialysis due to end-stage renal failure will be excluded
• subjects with evidence on history, physical or blood work of hepatic disease will be excluded since elevated serum transaminases are a potential adverse effect of acarbose
• cannot currently be taking an alpha-glucosidase inhibitor
• cannot have had allergic reactions to alpha-glucosidase inhibitors in the past
• Due to the fact that acarbose is renally excreted, all subjects must have a Creatine Clearance of greater than 25 ml/min
• Subjects with a past history of inflammatory bowel disease, intestinal obstruction, ileus and peptic ulcer disease will be excluded
• Subjects taking carbohydrate-splitting enzymes (such as amylase) will be excluded
• Subjects with chronic respiratory issues requiring treatment will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Postprandial Hypotension (PPH); Screening Meal Test performed and subject does not meet criteria for Postprandial Hypotension (PPH).
Placebo Comparator: Placebo; Screening Meal Test performed and subject meets criteria for Postprandial Hypotension (PPH). At second Meal Test subject will receive a placebo and will take a placebo with the first bite of the next 3 meals.	Drug: Placebo; Placebo given prior to meal the standardized meal; Other Names: Bayer Material No: 02839265; Acarbose Placebo Tablet
Active Comparator: Acarbose; Screening Meal Test performed and subject meets criteria for Postprandial Hypotension. During the second Meal Test subject will receive Acarbose 50mg and will take Acarbose 25mg with first bite of each of the next 3 meals.	Drug: Acarbose; Acarbose 50 mg given during Meal Test and Acarbose 25 mg taken with first bite of the next 3 meals.; Other Names: Precose; Glucobay; Prandase; Alpha-glucosidase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The postprandial cardiovascular response to a standardized meal compared between subjects with and without PPH	The postprandial cardiovascular response (mesenteric blood flow, adrenergic response, cerebral blood flow) to a standardized meal will be compared between n=30 subjects with PPH and n= 30 subjects without PPH.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The postprandial glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP) response to a standardized meal compared between subjects with and without PPH	The postprandial GLP-1 and GIP response to a standardized meal compared between subjects with and without PPH	2 years
The postprandial cardiovascular response between the Acarbose group and the Placebo group will be compared.	The postprandial cardiovascular response (mesenteric blood flow, adrenergic response, cerebral blood flow) to a standardized meal between the Acarbose group and the Placebo group will be compared.	2.5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ambulatory blood pressure monitoring (Welch-Allyn, Ambulatory Blood Pressure Monitor(ABPM) 6100S) performed for 24 hours	Starting the day following each meal test, each subject with PPH will take either acarbose 25 mg po tid (prior to each meal) or placebo po tid for one day. During this 24 hour period, each subject will undergo 24 Hr-ABPM (starting at 7 ante meridian (AM) the following day). Each subject will have ambulatory blood pressure monitoring (Welch-Allyn, ABPM 6100S) performed for 24 hours. Each subject will carry a logbook to record time of activity and all meals. Each subject will be given a watch synchronized to the 24-hour blood pressure monitor.	1 day

Collaborators and Investigators

• Sponsor: Kenneth Madden
• Investigators: Principal Investigator: Kenneth M Madden, MD, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: July 22, 2013
• First Submitted That Met QC Criteria: July 30, 2013
• First Posted (Estimate): August 1, 2013

Study Record Updates

• Last Update Posted (Actual): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 26, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Elderly; Syncope; Falls; Acarbose; PPH (Post Prandial Hypotension)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Unconsciousness; Consciousness Disorders; Hypotension; Syncope; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Acarbose; Glycoside Hydrolase Inhibitors
• Other Study ID Numbers: H13-01316; G-13-0001812 (Other Grant/Funding Number: The Heart and Stroke Foundation of Canada (the Foundation))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No