Kisspeptin Influence on Glucose Homeostasis

The goal of this study is to learn about how a naturally occurring hormone called kisspeptin affects blood sugar and insulin levels.

Study Overview

• Status: Completed
• Conditions: Hypogonadism; Impaired Glucose Tolerance
• Intervention / Treatment: Drug: kisspeptin 112-121; Other: Insulin Resistance Test; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion/Exclusion Criteria:

History:

• normal pubertal development
• stable weight for previous three months
• no active illicit drug use,
• no history of a medication reaction requiring emergency medical care,
• no difficulty with blood draws.

Physical examination:

• systolic BP < 140 mm Hg, diastolic < 90 mm Hg,

Laboratory studies: (per MGH reference ranges)

• normal hemoglobin, unless hypogonadal then no lower than 0.5 gm/dL below the lower limit of the reference range for normal women (as men and women with hypogonadism have lower hemoglobin levels off of treatment)
• hemoglobin A1C < 6.5%
• BUN, creatinine not elevated
• AST, ALT < 3x upper limit of normal
• negative serum pregnancy test (for all women)
• no hyperlipidemia by fasting lipid panel

Additional Criteria by Study Population

Healthy Men:

• normal body mass index (BMI between 18.5-25)
• no history of chronic disease, except well controlled thyroid disease
• no recent use of prescription medications which interfere with metabolism or reproduction. Use of levothyroxine or seasonal allergy medications is acceptable.
• no history of diabetes in a first degree relative.

Healthy Women:

• normal body mass index (BMI between 18.5-25)
• no history of chronic disease, except well controlled thyroid disease,
• no recent use of prescription medications which interfere with metabolism or reproduction. Use of levothyroxine or seasonal allergy medications is acceptable.
• no history of diabetes in a first degree relative,
• no use of contraceptive pills, patches or vaginal rings within last 4 weeks.
• regular menstrual cycles

Postmenopausal Women:

• body mass index (BMI between 18.5-30)
• no history of chronic disease except thyroid disease, and osteoporosis,
• no recent use of prescription medications which interfere with metabolism or reproduction. Use of levothyroxine, osteoporosis medications or seasonal allergy medications is acceptable,
• no history of diabetes in a first degree relative,
• normal activate protein C resistance screen,
• if applicable, able to undergo appropriate washout from hormone therapy.

Men and Women with Impaired Glucose Tolerance (IGT):

• diagnosis of impaired glucose tolerance by oral glucose tolerance test,
• all medical conditions well-controlled.

Men and Women with Hypogonadism

• diagnosis of hypogonadism,
• all other medical conditions well-controlled,
• if applicable, able to undergo appropriate washout from hormone therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kisspeptin and Insulin Resistance Test; Intravenous (IV) administration of kisspeptin 112-121; eat a standard mixed meal or drink a standard mixed meal or 75 grams of oral glucose	Drug: kisspeptin 112-121; Dose: 0.313-12.5 mcg/kg Duration: up to 16 hours; Other Names: metastin 45-54; Other: Insulin Resistance Test; Eat or drink a standard meal OR drink a standard drink containing 75 grams of sugar
Placebo Comparator: Placebo and Insulin Resistance Test; IV administration of fluids that contain no study drug; eat a standard mixed meal or drink a standard mixed meal or 75 grams of oral glucose	Other: Insulin Resistance Test; Eat or drink a standard meal OR drink a standard drink containing 75 grams of sugar; Other: Placebo; Receive IV fluids for up to 16 hours that do not contain any study drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average difference in area under the curve of insulin in response to a mixed meal tolerance test	Compares difference on and off kisspeptin	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average difference in area under the curve of glucose in response to a mixed meal tolerance test	Compares difference on and off kisspeptin	4 hours
Average difference in area under the curve of glucagon-like peptide 1 in response to a mixed meal tolerance test	Compares difference on and off kisspeptin	4 hours

Collaborators and Investigators

• Sponsor: Stephanie B. Seminara, MD
• Investigators: Principal Investigator: Margaret Lippincott, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2017
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): November 30, 2019

Study Registration Dates

• First Submitted: November 1, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (Estimated): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: kisspeptin; insulin regulation in pregnancy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Hyperglycemia; Glucose Intolerance; Hypogonadism; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 2016P001769

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After primary results are published, the authors will provide individuals participant data upon request as long as it does not conflict with state or Institutional regulations.

Drug and device information, study documents

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