MINDD: Metformin, Vitamin D, and Depression in Polycystic Ovary Syndrome (PCOS) Trial

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03380091
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Actual Duration (Months): 20.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Open-label randomized clinical trial assessing the efficacy of Metformin versus Vitamin D in improving symptoms of depressed mood in polycystic ovary syndrome.

Condition or Disease	Intervention/Treatment	Phase
PCOS; Depression; Vitamin D Deficiency; Insulin Resistance	Drug: Metformin; Drug: Vitamin D	Phase 4

Detailed Description

This is a single center, open-label, randomized, pilot clinical trial. Women with polycystic ovary syndrome and depressed mood, who are insulin resistant and vitamin D insufficient are eligible. Subjects are randomly assigned to one of two interventions: Vitamin D versus metformin. Subjects are followed with questionnaires and a final wrap-up clinic visit with a physician. The study duration is 12 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metformin, Vitamin D, and Depression in Polycystic Ovary Syndrome (PCOS) Trial: The MINDD Trial
• Actual Study Start Date: Dec 12, 2017
• Actual Primary Completion Date: Sep 1, 2019
• Actual Study Completion Date: Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin Metformin 1000 mg PO bid	Drug: Metformin; Oral medication daily; Other Names: Glucophage Glucophage XR Fortamet Glumetza
Experimental: Vitamin D (Cholecalciferol) Cholecalciferol 5,000 IU PO daily	Drug: Vitamin D; Oral medication daily; Other Names: Cholecalciferol

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Depression Score on the Beck Depression Inventory (BDI-II) at 12 Weeks [Baseline & 12 weeks]

   BDI-II is a validated self-reported instrument of 21 questions which are each scored 0-3. Total scores range from 0-63, with higher score totals indicating more severe depression symptoms. {0-9: indicates minimal depression; 0-18: indicates mild depression; 19-29: indicates moderate depression; 30-63: indicates severe depression}. Change = Week 12 total score - Baseline week score

Secondary Outcome Measures

1. Changes From Baseline Week in Insulin Resistance Score at Week 12. [Baseline week & week 12]

   Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) will be used to calculate Insulin Resistance based on fasting glucose (mg/dL) and fasting insulin (μIU/mL) blood serum assays tested at Quest Diagnostics. HOMA-IR = Fasting Insulin (uIU/mL) x Fasting Glucose (mg/dL). Healthy range is between 0.5-1.4. Values below 1.0 indicate insulin sensitivity and are optimal. Values greater than 1.9 indicate clinically significant insulin resistance.

2. Change From Baseline in State-Trait Anxiety Inventory Score (STAI-S) at 12 Weeks [Baseline week & Week 12]

   STAI-S is a validated self-reported instrument of 20 questions. Range of scores for the State Anxiety (STAI-S) subtest is 20-80, the higher score indicating greater anxiety. A threshold point score of 39-40 has been suggested by recent literature to detect clinically significant symptoms. Change = Week 12 total score - Baseline week score

3. Changes From Baseline Week in Vitamin D 25-hydroxy Levels at Week 12. [Baseline week & week 12]

   Vitamin D, 25-hydroxy blood serum assays will be tested at Quest Diagnostics. Changes in values from baseline week to week 12 will be calculated. Reference ranges: optimal 30-100 ng/mL Insufficient 20-29 ng/mL deficient <20ng/mL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Polycystic Ovary Syndrome diagnosis (Rotterdam Criteria)

• Vitamin D insufficiency (serum Vitamin D <30 ng/mL)

• Insulin resistance

• Mild or greater severity of depression by Beck Depression Inventory-II

Exclusion Criteria:

• Current metformin use

• Vitamin D supplementation of > 50,000 IU following confirmation of Vitamin D insufficiency

• Insulin-dependent diabetes mellitus

• Pregnancy or breastfeeding

• Untreated hypothyroidism

• Current active substance abuse

• Other major medical comorbidity: renal or hepatic dysfunction, severe pulmonary

• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Center for Reproductive Health	San Francisco	California	United States	94158

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Heather Huddleston, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 2, 2019

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT03380091
• Other Study ID Numbers: 17-22550
• First Posted: Dec 20, 2017
• Last Update Posted: Feb 9, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of California, San Francisco: PCOS; Depression; Vitamin D; Insulin Resistance; Anxiety; Quality of life; Mood disorders
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Insulin Resistance; Vitamin D Deficiency; Depression; Depressive Disorder; Vitamin D; Cholecalciferol; Metformin

Study Results

Participant Flow

Pre-assignment Detail	Of the 5 participants that were enrolled in the trial, all were randomized and assigned to treatment arms. 3 were assigned to the Vitamin D supplement arm and 2 were assigned to the Metformin arm.

Arm/Group Title	Vitamin D (Cholecalciferol)	Metformin
Arm/Group Description	Cholecalciferol 5,000 IU PO daily Vitamin D: Oral medication daily	Metformin 1000 mg PO bid Metformin: Oral medication daily
Period Title: Overall Study
STARTED	3	2
Began Arm Treatment	1	1
COMPLETED	1	1
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Vitamin D (Cholecalciferol)	Metformin	Total
Arm/Group Description	Cholecalciferol 5,000 IU PO daily Vitamin D: Oral medication daily	Metformin 1000 mg PO bid Metformin: Oral medication daily	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 100%	1 100%	3 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 50%	1 100%	2 66.7%
Not Hispanic or Latino	1 50%	0 0%	1 33.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 50%	1 100%	2 66.7%
More than one race	1 50%	0 0%	1 33.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 150%	2 200%	5 166.7%
Fasting Insulin (μIU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μIU/mL]	14.2 (4.6)	32 (0)	20.13 (9.19)
Fasting Glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	90.5 (3.5)	83 (0)	88 (4.54)
Fasting Insulin Resistance (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.12 (0.92)	6.6 (0)	4.28 (1.80)
Vitamin D, 25 hydroxy (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	21.5 (2.5)	21 (0)	21.33 (2.05)
Beck Depression Inventory (BDI-II) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.5 (4.5)	18 (0)	20.33 (4.02)
State-Trait Anxiety Inventory Score (STAI-S) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	54.5 (3.5)	44 (0)	51 (5.71)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Depression Score on the Beck Depression Inventory (BDI-II) at 12 Weeks
Description	BDI-II is a validated self-reported instrument of 21 questions which are each scored 0-3. Total scores range from 0-63, with higher score totals indicating more severe depression symptoms. {0-9: indicates minimal depression; 0-18: indicates mild depression; 19-29: indicates moderate depression; 30-63: indicates severe depression}. Change = Week 12 total score - Baseline week score
Time Frame	Baseline & 12 weeks

Outcome Measure Data

Analysis Population Description

In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for Change in Depression from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 scores were available.

Arm/Group Title	Vitamin D (Cholecalciferol)	Metformin
Arm/Group Description	Cholecalciferol 5,000 IU PO daily Vitamin D: Oral medication daily	Metformin 1000 mg PO bid Metformin: Oral medication daily
Measure Participants	1	1
Mean (Standard Deviation) [score on a scale]	-8 (0)	7 (0)

2. Secondary Outcome

Title	Changes From Baseline Week in Insulin Resistance Score at Week 12.
Description	Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) will be used to calculate Insulin Resistance based on fasting glucose (mg/dL) and fasting insulin (μIU/mL) blood serum assays tested at Quest Diagnostics. HOMA-IR = Fasting Insulin (uIU/mL) x Fasting Glucose (mg/dL). Healthy range is between 0.5-1.4. Values below 1.0 indicate insulin sensitivity and are optimal. Values greater than 1.9 indicate clinically significant insulin resistance.
Time Frame	Baseline week & week 12

Outcome Measure Data

Analysis Population Description

In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for Change in Insulin Resistance from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 serum insulin and glucose test results were available.

Arm/Group Title	Vitamin D (Cholecalciferol)	Metformin
Arm/Group Description	Cholecalciferol 5,000 IU PO daily Vitamin D: Oral medication daily	Metformin 1000 mg PO bid Metformin: Oral medication daily
Measure Participants	1	1
Mean (Standard Deviation) [units on a scale]	0.81 (0)	-1.2 (0)

3. Secondary Outcome

Title	Change From Baseline in State-Trait Anxiety Inventory Score (STAI-S) at 12 Weeks
Description	STAI-S is a validated self-reported instrument of 20 questions. Range of scores for the State Anxiety (STAI-S) subtest is 20-80, the higher score indicating greater anxiety. A threshold point score of 39-40 has been suggested by recent literature to detect clinically significant symptoms. Change = Week 12 total score - Baseline week score
Time Frame	Baseline week & Week 12

Outcome Measure Data

Analysis Population Description

In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for a Change in Anxiety scores from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 scores were available.

Arm/Group Title	Metformin	Vitamin D (Cholecalciferol)
Arm/Group Description	Metformin 1000 mg PO bid Metformin: Oral medication daily	Cholecalciferol 5,000 IU PO daily Vitamin D: Oral medication daily
Measure Participants	1	1
Mean (Standard Deviation) [score on a scale]	0 (0)	10 (0)

4. Secondary Outcome

Title	Changes From Baseline Week in Vitamin D 25-hydroxy Levels at Week 12.
Description	Vitamin D, 25-hydroxy blood serum assays will be tested at Quest Diagnostics. Changes in values from baseline week to week 12 will be calculated. Reference ranges: optimal 30-100 ng/mL Insufficient 20-29 ng/mL deficient <20ng/mL
Time Frame	Baseline week & week 12

Outcome Measure Data

Analysis Population Description

In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for Change in Vitamin D serum levels from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 serum Vitamin D test results were available.

Arm/Group Title	Vitamin D (Cholecalciferol)	Metformin
Arm/Group Description	Cholecalciferol 5,000 IU PO daily Vitamin D: Oral medication daily	Metformin 1000 mg PO bid Metformin: Oral medication daily
Measure Participants	1	1
Mean (Standard Deviation) [mg/dL]	11 (0)	-5 (0)

Adverse Events

Time Frame	Study activity participation window of 12 weeks.
Adverse Event Reporting Description	AE and SAE definition meet clinicaltrials.gov definitions Investigators will carefully track serious adverse events and all of these events will be reported to the DSM at scheduled meetings. Grade 4 adverse events will be reported to the DSM within 24 hours of receipt by the Study Coordinator. Adverse events meeting IRB reporting criteria (adverse event that are definitely, probably, or possibly related to the research AND serious OR unexpected) will be reported within 5 working days.
Arm/Group Title	Vitamin D (Cholecalciferol)		Metformin
Arm/Group Description	Cholecalciferol 5,000 IU PO daily Vitamin D: Oral medication daily		Metformin 1000 mg PO bid Metformin: Oral medication daily
All Cause Mortality
	Vitamin D (Cholecalciferol)		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Serious Adverse Events
	Vitamin D (Cholecalciferol)		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D (Cholecalciferol)		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)

Limitations/Caveats

Feasibility of recruitment and participant completion determined to be too low to continue the study and the trial was terminated early, resulting in only 2 of the 5 enrolled participants completing the trial. This lead to only two subjects will full data and one subject with partial data being analyzed.

More Information

Certain Agreements

All Principal Investigators ARE 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.