Pioglitazone and Insulin Resistance in ADT

Prostate Cancer Clinical Trial

Official title:

Role of Pioglitazone Therapy in Management of Insulin Resistance Associated With Androgen Deprivation Therapy (ADT) in Patients With Prostate Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05098327
• Other study ID #: STUDY00005310
• Secondary ID: UL1TR001412
• Status: Withdrawn
• Phase: Phase 3
• Start date: August 1, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: August 2023
• Source: State University of New York at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to establish the mechanisms underlying insulin resistance (reduced insulin action that can lead to high blood sugar and maybe diabetes) in patients undergoing androgen deprivation therapy (ADT) for prostate carcinoma as well as to investigate the role of pioglitazone therapy in reduction/ reversal of that insulin resistance

Description:

This is a single-center, cross-sectional then prospective, randomized single-blinded study with 2 groups of subjects. One group will be men with prostate cancer in various stages of ADT and the other group will be men with prostate cancer not on ADT as control group.

Patients interested in participating who meet the inclusion/exclusion criteria and who agree to undergo blood draws and fat biopsy will be identified from the Genito-urinary oncology and urology clinics. These patients will be referred to the Diabetes and Endocrinology Research Center of WNY where they will undergo blood draws in fasting state.

On the screening day, participants will be asked to complete the informed consent, medical history and physical exam, and non-fasting blood draws (for CBC, CMP and HbA1c) prior to participating in the study. 30 ml of blood will be drawn at this visit.

Subjects who qualify and consent to take part in the study will be called in for the baseline study visit where they will undergo blood draws in fasting state. HOMA-IR method will be used to determine insulin resistance. Subcutaneous fat biopsies will be performed in all patients.

Within the ADT group, subjects will be assigned a number by a computerized simple random number generation program (Excel, Microsoft Inc.) and will be randomized (1:1) to receive either pioglitazone or placebo. The patient will be blinded to the treatment, however, the research team will not. Subjects will be given a 12 week supply of pioglitazone 30 mg or placebo pills containing cellulose that will take once a day in morning. Subjects who develop side effects (weight gain, pedal edema) on the 30 mg dose will be asked to reduce the dose to 15 mg.

Subjects will then return to the research center in 12 weeks for visit 2 where the fasting blood draws and subcutaneous fat biopsies will be performed again. The subjects will then be discharged from the study and follow with their physicians. Subject will receive a phone call after 1 and 4 weeks following start of treatment to collect any safety data. Patients will be instructed to call the research center anytime they have a question or side effects.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male, age =18 years of age.

2. Body Mass Index of > 25 kg/m2

3. Biopsy-confirmed prostate adenocarcinoma currently on androgen deprivation therapy (ADT) for minimum of 3 months for the ADT group and biopsy-confirmed prostate adenocarcinoma not on ADT for control group

5. Hemoglobin > 11 g/dL, Creatinine < 1.5x ULN and liver function tests < 2x ULN 6. Participant must be able to read, write, and understand the English language and be able to provide written consent 7. Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

1. Known clinically significant severe COPD, ischemic heart disease, congestive heart failure, and/or significant cardiac arrhythmias

2. Any patient with known diabetes (A1c > 6.4%) or an anti-diabetic drug

3. Any condition contraindicating additional blood collection beyond standard of care

4. Subjects with known allergy to lidocaine (this is used to anesthetize area for fat biopsy)

5. Subjects with known allergy to pioglitazone or other thiazolidinediones

6. Subjects with pioglitazone use in last 6 months

7. Subjects with congestive Heart Failure Class 3 or 4

8. Subjects with osteoporosis, including history of fragility fracture

9. Subjects with history of bladder cancer

10. Subjects on chronic use of androgens, or opiates in the last 6 months or with panhypopituitarism, congenital HH (hypogonadotropic hypogonadism), prolactinoma, head trauma

11. Unwilling or unable to follow protocol requirements

12. Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to undergo study procedures.

Related Conditions & MeSH terms

• Androgen Deficiency
• Diabetes Mellitus, Type 2
• Insulin Resistance
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Pioglitazone 30 mg
pioglitazone 30 mg dose 1 tab daily will be given for 12 weeks
• Placebo
placebo pills containing cellulose 1 pill daily will be given for 12 weeks

Locations

Country	Name	City	State
United States	Diabetes and Endocrinology Research Center of WNY	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
State University of New York at Buffalo	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HOMA-IR	Change in HOMA-IR (the main index for evaluating insulin resistance) following pioglitazone and placebo treatment.	12 weeks
Secondary	IRS-1 serine phosphorylation	Determine levels of IRS-1 serine phosphorylation in adipose tissue and MNC as a molecular marker of inflammation induced insulin resistance at baseline and after pioglitazone and placebo treatments	12 weeks
Secondary	IRß	Changes in expression of insulin signaling gene (IRß) in both adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	IRS-1	Changes in expression of insulin signaling gene (IRS-1) in both adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	AKT-2	Changes in expression of insulin signaling gene (AKT-2) in both adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	GLUT-4	Changes in expression of GLUT-4 in adipose tissue between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	TNF-a	Changes in expression of proinflammatory gene (TNF-a) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	IL 1ß	Changes in expression of proinflammatory gene (IL 1ß) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	IKK-ß	Changes in expression of proinflammatory gene (IKK-ß) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	SOCS-3	Changes in expression of proinflammatory gene (SOCS-3) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	PTB-1B	Changes in expression of proinflammatory gene (PTB-1B) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	JNK-1	Changes in expression of proinflammatory gene (JNK-1) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks
Secondary	TLR-4	Changes in expression of proinflammatory gene (TLR-4) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group	12 weeks