Clinical trial NCT04958109
Conditions: Metabolic Diseases
Sponsor: Massachusetts General Hospital
Start date: 2021-10-28; Completion date: 2022-10-31
Enrollment: 16 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The goal of this study is to understand how exogenous kisspeptin affects metabolism by evaluating responses to an oral glucose tolerance test

Detailed description:
Assignment: Each study subject will serve as their own control. The order of the visits will be randomized.

Delivery of Interventions:

* Prior to the study visit, subjects will undergo a review of their medical history and screening laboratories.
* During the inpatient study, the subjects will

  * Undergo a 16-hour kisspeptin infusion
  * Undergo an oral glucose tolerance test

Arms: arm 1: • Intravenous administration of kisspeptin 112-121 x 16 hours arm 2: • Intravenous administration of placebo x 16 hours
Interventions: intervention 1: Oral Glucose Tolerance Test intervention 2: Kisspeptin intervention 3: Placebo
Intervention descriptions: intervention 1: Administration of a 75 gm oral glucose tolerance test intervention 2: Intravenous administration of kisspeptin 112-121 x 16 hours intervention 3: Intravenous administration of Placebo 16 hours

Protocol documents:
Prot_SAP_000.pdf: 
COVER PAGE 
 
Evaluation of Kisspeptin Glucose-
Stimulated Insulin Secretion With 
Oral Glucose Tolerance Test 
 
Clinical Trials ID: NCT04958109 
 
Date: 07/11/2024 
 
 
 
 
 


Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Oral Glucose Tolerance Test 
 
Inclusion/Exclusion Criteria: 
No PI concern about study subject appropriateness for study 
History:  
• 
over the age of 17,  
• 
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.  
• 
no history of hypertension, diabetes, heart disease, high cholesterol, cancer, or clotting disorders. 
• 
no history of chronic disease that has required hospitalization 
• 
no recent use of prescription medications which interfere with metabolism or reproduction (recent 
= within 5 half-lives of the drug), unless specified in the protocol (see below re: hormonal 
methods of birth control). Use of levothyroxine or seasonal allergy medications is acceptable, 
• 
no history of diabetes in a first degree relative, 
• 
Use of contraceptive pills and IUDs are acceptable if subject has been on them for >4 weeks at 
time of screening. 
o 
If applicable, subjects must be on this method of birth control 4 weeks prior to first clinical 
research center visit and continue use of it throughout all study procedures. 
Physical examination: 
• 
systolic BP < 140 mm Hg, diastolic < 90 mm Hg,  
• 
normal body mass index (BMI between 18.5-25) 
• 
regular menstrual cycles  
 
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 
• 
no hyperlipidemia by fasting lipid panel 
• 
negative serum pregnancy test (for all women) 
 
Subject Protocol 
 
Screening 
Healthy subjects who may have higher risk of a reaction to kisspeptin will be excluded. These include 
subjects who have a history of a severe allergic reaction, or who have abnormal physical exam or 
laboratory findings.  
 
Study Visits 
Clinical research center visits will only be done at MGH.  Following screening and eligibility determination, 
women will undergo the following protocol: 
i) 
DEXA scan (can be combined with any other visit) 
ii) 
admission to Clinical Research Center: 
a. frequent blood sampling  
b. standard dinner meal 
c. appetite questionnaires (before and during infusion) 
d. 12 hour fast 
e. kisspeptin administration (infusion) or placebo administration (infusion) 
f. 
undergo a oral glucose tolerance test  
g. frequent blood sampling to assess response to kisspeptin 


h. questionnaire on hunger and satiety 
iii) 
follow-up within 72 hrs of discharge (phone or email) 
iv) 
second admission to Clinical Research Center (as above) 
v) 
follow-up within 72 hrs of discharge (phone or email) 
 
Risks 
The risks involved with this study are associated with the administration of study drugs, frequent blood 
sampling, and DEXA scan. There are no known risks associated with kisspeptin administration. 
 
Blood Draws, including IVs: 
There is a slight discomfort associated with the placement of IV lines and a small risk of infection at blood 
draw sites. Subjects may faint from blood drawing or develop bruise or irriation at the site of the blood 
draw. An IV line may fail and a replacement IV will be placed, if possible. In addition, it is possible that 
subjects could develop anemia and related fatigue from blood-drawing. Subjects will be instructed to 
avoid donating blood or having large blood draws for 8 weeks after the overnight studies.  
 
DEXA Scan: 
As a result of your participation in this study you will be exposed to radiation from the whole body DEXA 
scan.  Please note that this radiation is not necessary for your medical care and is for research purposes 
only.  
 
The total amount of radiation exposure you will receive from taking part in this study is equal to a whole 
body exposure of about 8.40 microSieverts (µSv). A µSv is a unit of radiation dose. This amount of 
radiation is about the same as you would normally get in 1 day from natural background sources from the 
earth and the sky.  Scientists disagree on whether radiation doses at these low levels are harmful. A 
possible effect that could occur at doses used in this study is a slight increase in the risk of developing 
cancer later in life. 
 
Oral Glucose Tolerance Test:  The drink may taste very sweet making it hard to drink. Subjects may feel 
sick after drinking the glucose liquid and may vomit. There is a risk of hypoglycemia or symptoms of 
hypoglycemia without low blood sugar levels. These symptoms include weakness, hunger, sweating, and 
feeling nervous or restless. If subjects develop these symptoms during the test, their blood glucose level 
will be checked by glucometer. If the level is <60 mg/dL with symptoms, the subjects will be provided with 
glucose tabs and the study will be stopped. 
 
Statistical Analysis Plan:  
 
 
For OGTT, these estimates were generated using published data on reproducibility available for the 
primary endpoint1. In addition, the oral glucose insulin sensitivity index (OGIS) declines by 17% when 
comparing individuals with obesity to those who are lean, and by 26% when comparing individuals with 
impaired glucose tolerance to those without2. Therefore, with a clinically meaningful change of 10%, 
completion of these studies with 10 individuals under each condition is anticipated to provide a well-
powered study. 
 
References 
1. 
Gordon BA, Fraser SF, Bird SR, Benson AC. Reproducibility of multiple repeated oral glucose 
tolerance tests. Diabetes research and clinical practice 2011;94:e78-82. 
2. 
Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ. A model-based method for assessing insulin 
sensitivity from the oral glucose tolerance test. Diabetes care 2001;24:539-48.