Statin Monotherapy for Treatment of Endocrine Metabolic Disease Risk

NCT ID: NCT03113994

Last Updated: 2021-10-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-26

Study Completion Date

2022-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Rationale: Individuals with motor-complete spinal cord injury (SCI) undergo dramatic changes in body composition in the first 18 months post-injury, including declines in bone mineral density (BMD) that increase lower-extremity fragility fracture risk, and increases in fat mass that increase cardio-metabolic disease (CMD) risk. While statins are an effective treatment for dyslipidemia, research evidence suggests additional pleiotropic effects on bone through promotion of osteogenesis, suppression of osteoblast apoptosis, and inhibition of osteoclastogenesis. There are currently no effective therapies to treat sublesional osteoporosis (SLOP) and reduce the risk of fragility fractures in individuals with SCI.

Hypothesis: Twelve months of statin therapy with concurrent coenzyme Q10 (CoQ10), to reduce risk of statin neuromyotoxicity, and standard care (calcium 1250mg OD and vitamin D3 2000IU OD) will be superior to placebo with CoQ10 and standard care, for augmenting knee region BMD and reducing inflammatory stress (hs-CRP), thereby reducing endocrine metabolic disease risk.

Objective: To determine the safety and efficacy of statin therapy for augmenting distal femoral BMD among adults with chronic motor-complete SCI in Toronto, Ontario and Miami, Florida.

Study Design: Multi-centre, double-blind, randomized controlled Phase II safety and efficacy trial.

Subjects: Consenting men and premenopausal women (N=54, age 18-60 yrs) with chronic (≥2 years) spinal cord injury with a neurological level between C1-T10 and an AIS category of A/B.

Intervention: Rosuvastatin 10 mg po daily at night versus placebo for 12 months. All subjects will receive osteoporosis standard care (calcium carbonate 1250mg po daily and vitamin D3 2000 IU po daily) to maintain bone mass and CoQ10 100mg po daily to prevent statin-induced myopathy.

Outcomes: Primary safety outcomes: i) establish the safety of rosuvastatin in chronic SCI by reporting the frequency of myotoxicity and type II diabetes onset; ii) frequency and mean duration of liver transaminase elevations in the rosuvastatin and placebo groups. Primary efficacy outcome: measure the mean between group absolute changes in distal femur areal BMD (aBMD, g/cm2) from baseline to one year. Secondary efficacy outcomes: will examine the mean absolute changes from baseline in: i) volumetric BMD (vBMD, g/cm3); ii) markers of bone turnover - Bone Specific Alkaline Phosphatase (BALP), telopeptide (CTX), Sclerostin and RANK Ligand (RANK-L); iii) serum inflammatory markers including high sensitivity C-reactive Protein (hs-CRP), Interleukin-1ß (IL-1ß). interleukin-6 (IL-6), tumor necrosis factor - alpha (TNF-alpha), erythrocyte sedimentation rate (ESR); and, iv) lipid profile; low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides, and total cholesterol Clinical Implications: Should rosuvastatin prove to be safe and efficacious for reducing endocrine metabolic disease risk for adults with chronic SCI, the results will advance the health of people with SCI by reducing the frequency and severity of heart disease and fracture as they age, with a single intervention.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Spinal Cord Injuries Osteoporosis Metabolic Syndrome

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Rosuvastatin

Group Type ACTIVE_COMPARATOR

Rosuvastatin Calcium

Intervention Type DRUG

10mg Rosuvastatin, daily for 12 months

Coenzyme Q10

Intervention Type DIETARY_SUPPLEMENT

100mg CoQ10, daily for 12 months

Calcium Carbonate

Intervention Type DIETARY_SUPPLEMENT

1250mg Calcium Carbonate, daily for 12 months

Vitamin D

Intervention Type DIETARY_SUPPLEMENT

2000IU Vitamin D, daily for 12 months

Placebo

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Placebo, daily for 12 months

Coenzyme Q10

Intervention Type DIETARY_SUPPLEMENT

100mg CoQ10, daily for 12 months

Calcium Carbonate

Intervention Type DIETARY_SUPPLEMENT

1250mg Calcium Carbonate, daily for 12 months

Vitamin D

Intervention Type DIETARY_SUPPLEMENT

2000IU Vitamin D, daily for 12 months

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Rosuvastatin Calcium

10mg Rosuvastatin, daily for 12 months

Intervention Type DRUG

Placebo Oral Tablet

Placebo, daily for 12 months

Intervention Type DRUG

Coenzyme Q10

100mg CoQ10, daily for 12 months

Intervention Type DIETARY_SUPPLEMENT

Calcium Carbonate

1250mg Calcium Carbonate, daily for 12 months

Intervention Type DIETARY_SUPPLEMENT

Vitamin D

2000IU Vitamin D, daily for 12 months

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Adult (age 18-60 years)
* Motor complete SCI (C1-T10 AIS A/B)
* 2 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

Exclusion Criteria

* 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).
* History of heart attack or stroke.
* Untreated hypertension defined as: elevated BP above (135/85mmHg) assessed with an automated blood pressure cuff at 3 distinct time points in a 7-10 day period.(125, 126)
* Current alcohol or street drug abuse.
* Any illness or condition interfering with the trial conduct or subject safety.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

The Craig H. Neilsen Foundation

OTHER

Sponsor Role collaborator

Toronto Rehabilitation Institute

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role collaborator

University of Miami

OTHER

Sponsor Role collaborator

Rick Hansen Institute

OTHER

Sponsor Role collaborator

Dr. B. Catharine. Craven

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Dr. B. Catharine. Craven

Clinician Scientist/Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

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

Role: PRINCIPAL_INVESTIGATOR

Toronto Rehabilitation Institute - UHN

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University Of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

University Health Network - Toronto Rehab Lyndhurst Centre

Toronto, Ontario, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2016-350642

Identifier Type: -

Identifier Source: org_study_id