YOH1: Randomized Study of Yohimbine Treatment for Type 2 Diabetes Patients Carrying a Specific Genetic Risk Variant

• Sponsor: Anders Rosengren, MD PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01593215
• Collaborator: Region Skane (Other), Lund University (Other)
• Enrollment: 50
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The investigators have recently discovered a genetic variant in an adrenergic receptor that leads to increased risk for type 2 diabetes. The investigators have also seen that blockers of that receptor improves impaired insulin secretion in animals. The investigators will now test the blocker in patients with type 2 diabetes with or without the risk variant in an effort to make diabetes treatment more individualized.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Yohimbine	Phase 2

Detailed Description

We have recently discovered a genetic variant in an adrenergic receptor that leads to increased risk for type 2 diabetes. We have also seen that blockers of that receptor improves impaired insulin secretion in animals. We will now test the blocker in patients with type 2 diabetes with or without the risk variant in an effort to make diabetes treatment more individualized. Patients will receive two different doses of the blocker and the effect will be measured with oral glucose tolerance tests. The study is a randomized placebo-controlled study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Study of Yohimbine Treatment for Type 2 Diabetes Patients Carrying a Specific Genetic Risk Variant
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Placebo first then yohimbine placebo first, then yohimbine	Drug: Yohimbine; Yohimbine capsule
Active Comparator: Yohimbine first then placebo Yohimbine first then placebo	Drug: Yohimbine; Yohimbine capsule

Outcome Measures

Primary Outcome Measures

1. Insulin Secretion [30 minutes after oral glucose]

   insulin secretion will be measured (nMole) in response to an oral glucose tolerance test. Patients will receive the capsules 1 h before the glucose test, and the insulin levels 30 minutes after the oral glucose will be used as a primary outcome measure. The insulin levels at the highest tolerated dose of yohimbine will be used.

Secondary Outcome Measures

1. Glucose [30 minutes after oral glucose]

   Plasma glucose will be measure (mMole) in response to an oral glucose tolerance test. Patients will receive the capsules 1 h before the glucose test, and the glucose levels 30 minutes after the oral glucose will be used as a secondary outcome measure. The glucose levels at the highest tolerated dose of yohimbine will be used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• type 2 diabetes

• informed consent

• age 18-70, for females only postmenopausal

Exclusion Criteria:

• heart disease

• anxiety disorder

• antidiabetic treatment other than metformin

• adrenergic blockers

• ulcus

• allergy to any component in the capsules

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Skanes Universitetssjukhus	Malmo	Skane	Sweden	20502

Sponsors and Collaborators

• Anders Rosengren, MD PhD
• Region Skane
• Lund University

Investigators

• Principal Investigator: Anders Rosengren, MD PhD, Region Skane

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anders Rosengren, MD PhD, MD PhD, Region Skane
• ClinicalTrials.gov Identifier: NCT01593215
• Other Study ID Numbers: 2010-018604-85
• First Posted: May 8, 2012
• Last Update Posted: Jan 9, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Anders Rosengren, MD PhD, MD PhD, Region Skane: genetics; type 2 diabetes; insulin secretion
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Yohimbine

Study Results

Participant Flow

Arm/Group Title	Placebo First Then Yohimbine	Yohimbine First Then Placebo
Arm/Group Description	Placebo first, then 2 weeks washout and then yohimbine	Yohimbine first, 2 weeks washout and then placebo
Period Title: Overall Study
STARTED	25	25
COMPLETED	24	25
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Placebo First Then Yohimbine	Yohimbine First Then Yohimbine	Total
Arm/Group Description	placebo first Yohimbine: Yohimbine capsule	Yohimbine first and then placebo	Total of all reporting groups
Overall Participants	25	25	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61 (8)	60 (7)	60 (8)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 84%	21 84%	42 84%
>=65 years	4 16%	4 16%	8 16%
Sex: Female, Male (Count of Participants)
Female	5 20%	3 12%	8 16%
Male	20 80%	22 88%	42 84%
Region of Enrollment (participants) [Number]
Sweden	25 100%	25 100%	50 100%

Outcome Measures

1. Primary Outcome

Title	Insulin Secretion
Description	insulin secretion will be measured (nMole) in response to an oral glucose tolerance test. Patients will receive the capsules 1 h before the glucose test, and the insulin levels 30 minutes after the oral glucose will be used as a primary outcome measure. The insulin levels at the highest tolerated dose of yohimbine will be used.
Time Frame	30 minutes after oral glucose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Yohimbine
Arm/Group Description	placebo Yohimbine: Yohimbine capsule	Yohimbine Yohimbine: Yohimbine capsule
Measure Participants	49	49
Mean (95% Confidence Interval) [% increase of Ins30]	5	29

2. Secondary Outcome

Title	Glucose
Description	Plasma glucose will be measure (mMole) in response to an oral glucose tolerance test. Patients will receive the capsules 1 h before the glucose test, and the glucose levels 30 minutes after the oral glucose will be used as a secondary outcome measure. The glucose levels at the highest tolerated dose of yohimbine will be used.
Time Frame	30 minutes after oral glucose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Placebo		Yohimbine
Arm/Group Description	placebo Yohimbine: Yohimbine capsule		Yohimbine Yohimbine: Yohimbine capsule
All Cause Mortality
	Placebo		Yohimbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Yohimbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		1/49 (2%)
Psychiatric disorders
Anxiety	0/49 (0%)		1/49 (2%)
Vascular disorders
Transitory ischemic attack	0/49 (0%)		1/49 (2%)
Other (Not Including Serious) Adverse Events
	Placebo		Yohimbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		6/49 (12.2%)
Psychiatric disorders
Anxiety	0/49 (0%)	0	6/49 (12.2%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.