Statin Monotherapy for Treatment of Endocrine Metabolic Disease Risk

NCT03113994 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 2016-350642
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 2

Brief Summary

Rationale: After having a spinal cord injury (SCI), people develop changes in their body composition that influences their long-term health. Individuals with paralysis after SCI will have large declines in their bone density ant increases in fat mass which increases their risk of fracture and heart disease. Therapies to prevent SCI-related changes in body composition and their health effects are needed. Drugs known as "statins" used often to reduce high cholesterol, may help to reduce bone loss and inflammation. Hypothesis: Among adults with SCI for a long time, treatment with a drug named Rosuvastatin or a sugar pill, with supplements (coenzyme Q10, calcium and vitamin D), for twelve months can decrease their endocrine metabolic disease risk by increasing bone density and reducing inflammation. Study Design: A clinical trial will be conducted in Toronto, Ontario and Miami, Florida. Subjects will get statin therapy or placebo (sugar pill) by chance. Study subjects and research staff will not know whether they are taking the study drug or a sugar pill until after the study Subjects: Fifty-four adults (age 18-60 years) with a long-term SCI and no movement below their level of injury. Treatment: Subjects will be prescribed Rosuvastatin 10 mg daily or a sugar pill. In addition, all subjects will receive 100 mg of Co-Q10 daily, calcium carbonate 1250 mg and, vitamin D 2,000 IU once a day. Data Collected: Subjects' bone density will be collected at the start and end of the study. Change in bone density between the two groups will be compared to see if one is better. Blood samples will be collected quarterly to make sure subjects are safe and do not develop problems with their liver or muscles and to measure the effects of the study drugs on inflammation throughout the body. Clinical Implications: Statins may be safe and effective therapy for adults living with SCI who are at increased risk of endocrine metabolic disease as they age.

Conditions

Spinal Cord Injuries; Osteoporosis; Metabolic Syndrome

Keywords

Spinal Cord Injury; Osteoporosis; Cardiometabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in areal BMD of the knee region

  Dual Xray Absorptiometry (DXA) Assessment of areal bone mineral density (aBMD) of the knee region

  Baseline and 12 months (or study completion)

Secondary Outcomes (15)

• Change from Baseline in Low density lipoprotein cholesterol (LDL)

  Baseline and 12 months (or study completion)

• Change from Baseline in high density lipoprotein cholesterol (HDL)

  Baseline and 12 months (or study completion)

• Change from Baseline in triglycerides (TG)

  Baseline and 12 months (or study completion)

• Change from Baseline in total cholesterol

  Baseline and 12 months (or study completion)

• Change from Baseline in High sensitivity C-reactive Protein (hsCRP)

  Baseline and 12 months (or study completion)

Other Outcomes (3)

• Changes in visceral adipose tissue

  Baseline and 12 months (or study completion)

• Changes in lean mass

  Baseline and 12 months (or study completion)

• Changes in aortic arterial stiffness

  Baseline and 12 months (or study completion)

Study Arms (2)

Rosuvastatin

ACTIVE COMPARATOR

Drug: Rosuvastatin Calcium; Dietary Supplement: Coenzyme Q10; Dietary Supplement: Calcium Carbonate; Dietary Supplement: Vitamin D

Placebo

PLACEBO COMPARATOR

Drug: Placebo Oral Tablet; Dietary Supplement: Coenzyme Q10; Dietary Supplement: Calcium Carbonate; Dietary Supplement: Vitamin D

Interventions

Rosuvastatin Calcium DRUG

10mg Rosuvastatin, daily for 12 months

Rosuvastatin

Placebo Oral Tablet DRUG

Placebo, daily for 12 months

Placebo

Coenzyme Q10 DIETARY_SUPPLEMENT

100mg CoQ10, daily for 12 months

Placebo; Rosuvastatin

Calcium Carbonate DIETARY_SUPPLEMENT

1250mg Calcium Carbonate, daily for 12 months

Placebo; Rosuvastatin

Vitamin D DIETARY_SUPPLEMENT

2000IU Vitamin D, daily for 12 months

Placebo; Rosuvastatin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult (age 18-60 years)
• Motor complete SCI (C1-T10 AIS A/B)
• years post-injury
• Have a telephone, and ability to attend the study visits
• Able to take oral medications and swallow independently
• Can provide free and informed consent
• Ability to understand instructions in English
• May report current use of oral alendronate 10mg daily or 70mg weekly or risedronate 5mg daily, 30mg weekly or 150mg monthly

You may not qualify if:

• Current and/or one year prior to enrolment treatment with any statin such as atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, simvastatin and rosuvastatin.
• Current treatment with IV bisphosphonate, denosumab, recombinant PTH, ovarian hormone therapy, an oral contraceptive, Immunosuppressants (Including Cyclosporine) and fusidic acid.
• Known allergy to Rosuvastatin, lactose powder, CoQ10, calcium carbonate, vitamin D2 and vitamin D3, or any other ingredient found in rosuvastatin, placebo or study supplements.
• History of Paget's disease, osteomalacia, steroid induced osteoporosis, or untreated parathyroid or untreated thyroid disease.
• Subjects with history of stage 4 chronic kidney disease. (124)
• Current Weight ≥136 kg.
• Bilateral knee region metal implants (hardware), history of bilateral knee region contracture \>30 degrees, fracture or any other bilateral knee region pathology which would preclude accurate DXA assessment of one limb.
• Post-menopausal women (absence of menses for a minimum of 1 year).
• Women with amenorrhea due to bilateral surgical removal of the ovaries and/or uterus (women with amenorrhea due to spinal cord injury are able to participate).
• Pregnancy or lactation.
• Female of child-bearing potential who is engaged in active heterosexual relations and is not using appropriate birth control methods. Appropriate methods of birth control will include: surgical sterilization at least 6 months prior to using study drug or sexual activity restricted to a vasectomized partner, barrier contraception with a condom or diaphragm in conjunction with spermicidal gel in use at least 30 days prior to using study drug OR sexual abstinence as a lifestyle.
• History of liver disease or abnormal Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT), ≥1.5 times the upper limit of the normal reference range at enrolment.
• History of symptomatic hypocalcemia or hypophosphatemia.
• Concurrent treatment with prednisone (\>7.5mg/day for 90 days).
• Vitamin D deficiency (Serum Vitamin D level \<75nmol/L) after completing 8 to 12 weeks of treatment for Vitamin D deficiency as per the Vitamin D correction protocol (Appendix Page 1).

Sponsors & Collaborators

• Dr. B. Catharine. Craven: lead
• The Craig H. Neilsen Foundation: collaborator
• Toronto Rehabilitation Institute: collaborator
• University Health Network, Toronto: collaborator
• University of Miami: collaborator
• Rick Hansen Institute: collaborator

Study Sites (2)

University Of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University Health Network - Toronto Rehab Lyndhurst Centre

Toronto, Ontario, M4G 3V9, Canada

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Osteoporosis; Metabolic Syndrome

Interventions

Rosuvastatin Calcium; coenzyme Q10; Calcium Carbonate; Vitamin D

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• B. Catharine Craven, BA, MD, FRCPC, MSc

  Toronto Rehabilitation Institute - UHN

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinician Scientist/Principal Investigator

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: April 14, 2017
• Study Start: February 26, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (1)