Vigabatrin and Insulin Sensitivity

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Спонсори

Washington University School of Medicine

КЛИНИЧНО ИЗСЛЕДВАНЕ: NCT04321395

BioSeek: nct04321395

Ключови думи

non-alcoholic fatty liver disease

Резюме

Nonalcoholic fatty liver disease (NAFLD) is a common complication of obesity and is associated with an increased risk of developing type 2 diabetes. The hallmark feature of NAFLD is an increase in intrahepatic triglyceride (IHTG) content. Data from studies conducted in rodent models suggest increased IHTG content can alter hepatic vagal afferent nerve (HVAN) activity. In rodent models of obesity and NAFLD, HVAN activity is reduced leading to impaired insulin sensitivity and glucose control. The reduction in HVAN activity is likely due to increased hepatic release of GABA, an inhibitory neurotransmitter, attributable to increased expression of GABA-Transaminase (GABA-T). Pharmacological inhibition of GABA-T in obese mice by treatment with vigabatrin, an irreversible inhibitor of GABA-T improves glucose tolerance and reduces hyperinsulinemia, hyperglycemia, and insulin resistance. It is not known if vigabatrin can also improve metabolic function in people. We propose to conduct a randomized clinical controlled trial to determine the effect of vigabatrin on insulin sensitivity and oral glucose tolerance in adults with obesity and NAFLD.

Дати

Последна проверка:	02/29/2020
Първо изпратено:	03/22/2020
Очаквано записване подадено:	03/22/2020
Първо публикувано:	03/24/2020
Изпратена последна актуализация:	03/22/2020
Последна актуализация публикувана:	03/24/2020
Действителна начална дата на проучването:	05/31/2020
Приблизителна дата на първично завършване:	05/31/2022
Очаквана дата на завършване на проучването:	05/31/2023

Състояние или заболяване

NAFLD

Obesity

Интервенция / лечение

Drug: Vigabatrin

Drug: Placebo

Фаза

Фаза 2

Групи за ръце

Arm	Интервенция / лечение
Experimental: Vigabatrin	Drug: Vigabatrin Vigabatrin - Pill, 500 mg twice daily for 7 days (days 0-6), 1000 mg twice daily for 7 days (days 7-13), 1500 mg twice daily for 10 days (days 14-23), 1000 mg twice daily for 7 days (days 24-30), 500 mg twice daily for 7 days (days 31-37) and will discontinue treatment on day 38.
Placebo Comparator: Placebo	Drug: Placebo Pill, 1 pill twice daily for 7 days (days 0-6), 2 pills twice daily for 7 days (days 7-13), 3 pills twice daily for 10 days (days 14-23), 2 pills twice daily for 7 days (days 24-30), 1 pill twice daily for 7 days (days 31-37) and will discontinue on day 38.

Критерии за допустимост

Възрасти, отговарящи на условията за проучване	18 Years Да се 18 Years
Полове, допустими за проучване	All
Приема здрави доброволци	Да
Критерии	Inclusion Criteria: - age 25-60 years old - BMI 30.0-49.9 kg/m2 - IHTG content ≥5.6 - Homeostatic Model of Insulin Resistance (HOMA-IR) Score>2.5. Exclusion Criteria: - i) medical, surgical, or biological menopause; ii) previous bariatric surgery; iii) structured exercise ≥250 min per week (e.g., brisk walking); iv) unstable weight (>4% change during the last 2 months before entering the study); v) significant organ system dysfunction (e.g., diabetes, severe pulmonary, kidney or cardiovascular disease); vi) cancer; vii) polycystic ovary syndrome; viii) major psychiatric illness; ix) conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders); x) regular use of tobacco products; xi) excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women); xii) use of medications that are known to affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued for this study; xiii) pre-exisiting visual field deficits; xiv) pregnant or lactating women; xv) conditions that render subject unable to complete all testing procedures (e.g. aversion to needles, metal implants that prevent magnetic resonance imaging); xvi) persons who are unable or unwilling to follow the study protocol; and xvii) persons who are not able to grant voluntary informed consent

Резултат

Първични изходни мерки

1. Insulin Sensitivity [3 weeks after initiation of treatment]

Measured by hyperglycemic euglycemic clamp

Вторични изходни мерки

1. Oral Glucose Tolerance [3 weeks after initiation of treatment]

Measured by 75 gram oral glucose tolerance test

Vigabatrin and Insulin Sensitivity

Ключови думи

triglyceride

non-alcoholic fatty liver disease

захарен диабет тип 2

хипергликемия

инсулинова резистентност

hyperinsulinism

затлъстяване